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1.
Rev. bras. oftalmol ; 83: e0009, 2024. tab, graf
Article in Portuguese | LILACS | ID: biblio-1535599

ABSTRACT

RESUMO Objetivo: Avaliar o efeito do colírio de brimonidina 0,2% na redução da hiperemia e do sangramento ocular durante as cirurgias de estrabismo, em comparação com o colírio de nafazolina 0,025% + feniramina 0,3%. Métodos: Foram avaliados 14 pacientes com estrabismo e indicação de correção cirúrgica bilateral. Foi instilado antes do procedimento, de forma aleatória, um colírio em cada olho dos pacientes avaliados. A análise subjetiva da hiperemia conjuntival e do sangramento perioperatório foi realizada de forma duplo-cega, por dois cirurgiões. A avaliação objetiva do nível de hiperemia conjuntival foi realizada por análise das imagens obtidas por meio do software ImageJ®. Resultados: A análise de modelos multivariados de efeito misto indicou diferenças estatisticamente significantes entre os grupos em relação à hiperemia (avaliador 2) e ao sangramento intraoperatório (avaliadores 1 e 2), com maiores escores nos casos tratados com colírio de nafazolina + feniramina. Entretanto, não houve diferença estatística na análise objetiva realizada por meio da saturação de cores obtidas pelo programa ImageJ®. Conclusão: O colírio de brimonidina pode ser superior ao colírio de nafazolina + feniramina na redução do sangramento, levando-se em conta apenas a análise subjetiva.


ABSTRACT Objective: To evaluate the effect of 0.2% brimonidine eye drops in reducing hyperemia and ocular bleeding during strabismus surgeries, in comparison with 0.025% naphazoline + 0.3% pheniramine eye drops. Methods: Fourteen patients with strabismus and indication for bilateral surgical correction were evaluated. Before the procedure, the eye drops were instilled randomly in each eye of the evaluated patients. The subjective analysis of conjunctival hyperemia and perioperative bleeding was performed in a double-blind manner, by 02 surgeons. The objective assessment of the level of conjunctival hyperemia was performed by analyzing the images obtained using the ImageJ® software. Results: The analysis of multivariate mixed effect models indicated statistically significant differences between the groups in relation to hyperemia (rater 2) and intraoperative bleeding (raters 1 and 2) with higher scores in cases treated with naphazoline + pheniramine eye drops. However, there were no statistically significant differences in the objective analysis of color saturation obtained by the ImageJ® program. Conclusion: Brimonidine eye drops may be superior to naphazoline + pheniramine eye drops in reducing bleeding, taking into account the subjective analysis only.


Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Pheniramine/administration & dosage , Eye Hemorrhage/prevention & control , Strabismus/surgery , Brimonidine Tartrate/administration & dosage , Hyperemia/prevention & control , Intraoperative Complications/prevention & control , Naphazoline/administration & dosage , Ophthalmic Solutions/administration & dosage , Premedication , Ophthalmologic Surgical Procedures/methods , Vasoconstriction/drug effects , Photography , Double-Blind Method , Administration, Topical , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Hemostasis, Surgical/methods
2.
Rev. bras. cir. cardiovasc ; 33(6): 553-558, Nov.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-977479

ABSTRACT

Abstract Objective: The aim of this study was to compare the efficacy of two different papaverine concentrations (0.5 mg/ml and 2 mg/ml) for vasospasm prevention and their impact on endothelium integrity. Methods: We have studied distal segments of radial arteries obtained by no-touch technique from coronary artery bypass graft (CABG) patients (n=10). The vasodilatory effect of papaverine (concentrations of 0.5 mg/ml and 2 mg/ml) was assessed in vitro, in isometric tension studies using ex vivo myography (organ bath technique) and arterial rings precontracted with potassium chloride (KCl) and phenylephrine. The impact of papaverine on endothelial integrity was studied by measurement of the percentage of vessel's circumference revealing CD34 endothelial marker. Results: 2 mg/ml papaverine concentration showed stronger vasodilatatory effect than 0.5 mg/ml, but it caused significantly higher endothelial damage. Response to KCl was 7.35±3.33 mN for vessels protected with papaverine 0.5 mg/ml and 2.66±1.96 mN when papaverine in concentration of 2 mg/ml was used. The histological examination revealed a significant difference in the presence of undamaged endothelium between vessels incubated in papaverine 0.5 mg/ml (72.86±9.3%) and 2 mg/ml (50.23±13.42%), P=0.002. Conclusion: Papaverine 2 mg/ml caused the higher endothelial damage. Concentration of 0.5 mg/ml caused better preservation of the endothelial lining.


Subject(s)
Humans , Male , Female , Aged , Papaverine/administration & dosage , Vasodilator Agents/administration & dosage , Coronary Artery Disease/surgery , Endothelium, Vascular/drug effects , Radial Artery/drug effects , Coronary Vasospasm/prevention & control , Papaverine/adverse effects , Papaverine/pharmacology , Vasoconstriction/drug effects , Vasodilation/drug effects , Vasodilator Agents/adverse effects , Vasodilator Agents/pharmacology , Coronary Artery Disease/physiopathology , Coronary Artery Bypass/methods
3.
Rev. chil. cir ; 70(5): 425-431, 2018. graf, ilus
Article in Spanish | LILACS | ID: biblio-978009

ABSTRACT

Resumen Introducción: Prolongar la permeabilidad de los injertos utilizados en bypass coronario es un desafío constante. Objetivo: Comparar anatomofuncionalmente venas safenas humanas (VSH) extraídas con técnica convencional (TC) vs técnica "no-touch" (NT). Material y Método: Estudio experimental. Se diseccionó VSH con TC y NT en el pabellón de cirugía cardiaca del Hospital Regional de Antofagasta. Las muestras de VSH fueron seccionadas en anillos de 3 mm y conservados en cámaras de órganos aislados con solución Ringer-Krebs. Para evaluar la vasomotilidad se administró norepinefrina (10-6M), papaverina (10-4M), acetilcolina (10-6M) y nitroprusiato de sodio (10-5M). Un segmento de las muestras fue fijado en formalina al 10%, procesado con técnica histológica y analizado bajo microscopía óptica. Las muestras fueron teñidas con hematoxilina-eosina, Verhoeff y orceína. El análisis estadístico fue realizado mediante el software Prism Graphad. Resultados: Reactividad vascular: La vasoconstricción inducida por noradrenalina fue significativamente superior en anillos del grupo NT vs TC (p < 0,0001). La vasodilatación producida por papaverina y acetilcolina fue superior en el grupo NT (p < 0,004) y (p < 0,0003), respectivamente. Estudio morfométrico: El grupo NT presentó túnica muscular (0,755 vs 0,680 mm), adventicia (0,5600 vs 0,4663 mm) y pared total (1,344 vs 0,962 mm) más gruesa que el grupo TC. No hubo diferencias significativas respecto el número de vasa vasorum. Conclusión: El grupo NT responde significativamente mejor a estímulos vasoconstrictores y vasodilatadores. Los resultados se asocian con las diferencias morfométricas.


Introduction: Prolonging of the grafts permeability used in coronary bypass is a constant challenge. Objective: To compare anatomical and functional human saphenous veins (VSH) extracted "No touch" (NT) technique vs conventional technique (TC). Materials and Methods: Experimental study. VSH dissected with CT and NT in the Regional Hospital of Antofagasta cardiac surgery ward. VSH samples were sectioned into 3 mm rings and preserved in isolated organs chambers with Krebs-Ringer solution. To evaluate the vasomotor activity, norepinephrine (10-6M), papaverine (10-4M), acetylcholine (10-6M) and sodium nitroprusside (10-5M) was administered. A segment of samples was fixed in 10% formalin, processed and histological analyzed under light microscopy technique with hematoxylin-eosin, Verhoeff and orceína. Statistical analysis was performed using the Prism software Graphad. Results: Vascular Reactivity: norepinephrine-induced vasoconstriction was significantly higher in the group rings NT vs TC (p < 0.0001). Vasodilation was higher with papaverine and acetylcholine in the NT group (p < 0.004) and (p < 0.0003), respectively. Morphometric study: The NT group presented muscularis (0.755 vs 0.680 mm), adventitious (0.5600 vs 0.4663 mm), and total wall (1.344 vs 0.962 mm) thicker than the TC group. No significant differences in vasa vasorum number identified. Conclusion: The NT group vasoconstrictor and vasodilator responds significantly better. Results correlate with morphometric differences.


Subject(s)
Humans , Saphenous Vein/drug effects , Saphenous Vein/transplantation , Tissue and Organ Harvesting/methods , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , In Vitro Techniques , Coronary Artery Bypass
4.
Braz. j. biol ; 77(4): 781-786, Nov. 2017. tab, graf
Article in English | LILACS | ID: biblio-888808

ABSTRACT

Abstract Previous studies performed in marine fish (I. conceptionis and G. laevifrons) showed that indomethacin blocked arterial contraction mediated by acetylcholine (ACh). The objective of this study was to determine if contraction induced by acetylcholine is mediated by the cyclooxygenase pathway in several arterial vessels in the Chilean frog Calyptocephalella gayi. Arteries from the pulmonary (PA), dorsal (DA), mesenteric (MA) and iliac (IA) regions were dissected from 6 adult specimens, and isometric tension studies were done using dose response curves (DRC) for ACh (10-13 to 10-3 M) in presence of a muscarinic antagonist (Atropine 10-5 M) and an unspecific inhibitor of cyclooxygenases (Indomethacin, 10-5M). All the studied arteries exhibited vasoconstriction mediated by ACh. This vasoconstriction was abolished in the presence of atropine in DA, MA and IA and attenuated in PA. Indomethacin abolished the vasoconstriction in MA and attenuated the response in PA, DA and IA. Similar to marine fish, C. gayi have an ACh-mediated vasoconstrictor pattern regulated by muscarinic receptors that activate a cyclooxygenase contraction pathway. These results suggest that the maintenance in vasoconstrictor mechanisms mediated by ACh→COX →vasoconstriction is conserved from fish to frogs.


Resumo Estudos feitos em peixes marinhos (I. conceptionis e G. laevifrons) têm demostrado que a indometacina bloqueia a contração arterial mediada por acetilcolina (ACh). O objetivo do presente estudo foi avaliar o efeito da via da ciclooxigenase na contração induzida por ACh em vasos arteriais da rã chilena Calyptocephalella gayi. Foram dissecadas regiões das artérias pulmonares (PA), dorsal (DA), mesentérica (MA) e ilíaca (IA) de seis espécimes adultos e realizados estudos de tensão isométrica utilizando curvas dose-resposta (CDR) de ACh (10-13 a 10-3 M) na presença de um antagonista muscarínico (atropina, 10-5 M) e um inibidor das ciclooxigenases (indometacina, 10-5 M). Todas as artérias evidenciaram uma resposta vasoconstritora mediada por ACh. Esta resposta vasoconstrictora foi suprimida na presença de atropina nas artérias DA, MA, IA e atenuada na PA. A indometacina suprimiu a vasoconstrição na artéria MA e atenuou a resposta nas artérias PA, DA e IA. Tal como os peixes marinhos, a C. gayi tem um padrão de vasoconstrição mediado por Ach que é regulado pelos receptores muscarínicos e pela ciclooxigenase. Estes resultados sugerem a conservação dos mecanismos vasoconstrictores mediados por ACh→COX em peixes e rãs.


Subject(s)
Animals , Anura/physiology , Atropine/pharmacology , Vasoconstriction/drug effects , Indomethacin/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Muscarinic Antagonists/pharmacology , Arteries/drug effects , Acetylcholine/pharmacology , Chile , Prostaglandin-Endoperoxide Synthases/metabolism
5.
Rev. chil. pediatr ; 88(2): 280-284, abr. 2017. ilus
Article in Spanish | LILACS | ID: biblio-844612

ABSTRACT

Una adecuada dilatación pupilar es necesaria para evaluar a neonatos con riesgo de desarrollar enfermedades oftalmológicas. Sin embargo, este procedimiento no está libre de efectos adversos locales o sistémicos. La vasoconstricción local posterior a la aplicación de midriáticos es una de estas complicaciones, existiendo además descritos efectos secundarios sistémicos. OBJETIVO: Presentar complicaciones asociadas al uso de midriáticos en 2 recién nacidos sometidos a evaluación oftalmológica. CASO CLINICO 1: Recién nacido de término con diagnóstico prenatal de restricción de crecimiento intrauterino e hidrocefalia. Al 5º día de vida se solicitó evaluación oftalmológica por presencia de opacidades corneales. Al realizar el procedimiento se evidenció palidez periorbitaria, al igual que taquicardia e hipertensión arterial en las siguientes 2 horas post procedimiento. Estos efectos secundarios se resolvieron espontáneamente pocas horas después del procedimiento. CASI CLINICO 2: Neonato de pretérmino de 27 semanas de gestación con antecedentes de síndrome de dificultad respiratoria, ductus arterioso persistente, hemorragia intraventricular grado III e hidrocefalia severa. Se solicitó examen oftalmológico a los 28 días de vida por sospecha de retinopatía del prematuro. A los 10 minutos post administración de midriáticos se observó palidez periorbitaria bilateral sin deterioro de signos vitales, presentando 24 horas después intolerancia a la alimentación y distensión abdominal. Se descartó enterocolitis necrotizante. CONCLUSIÓN: Es necesario establecer protocolos clínicos en relación al uso de midriáticos para reducir efectos deletéreos en neonatos de alto riesgo, como son los prematuros y aquellos con hidrocefalia. Por lo tanto, la monitoría debería realizarse durante la evaluación.


Adequate pupil dilation is needed to evaluate some neonates at risk of developing illness during this stage. However, this procedure is not free of adverse effects, either local or systemic. One of these complications is the local vasoconstriction of the preterm baby’s skin following the application of mydriatic eye drops. OBJECTIVE: To describe secondary local and systemic complications of pharmacological pupil dilation in 2 newborns. CLINICAL CASE 1: Full term baby with diagnosis of low-birth weight and hydrocephalia. An ophtalmological evaluation was performed at 5 days of age due to the presence of corneal opacities. Peri ocular pallor was observed during the procedure, as well as tachycardia and hypertension 2 hours later, spontaneosly recovered. CASE 2: Preterm newborn, 27 weeks of gestational age. Neonatal respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage and hydrocephalia were diagnosed at birth. At 28 days of life an ophtalmological evaluation was performed. After 10 minutes of mydriatic drops administration to evaluate preterm retinopathy, peri ocular pallor was observed, with spontaneous resolution; however, 24 hours later, the patient showed abdominal distention and feeding intolerance. Necrotizing enterocolitis was discarded, and symptoms were spontaneosly recovered. CONCLUSION: The establishment of protocols in relation to the number of drops to apply for dilation is needed to reduce deleterious effects on high risk infants, such as premature babies and those with hydrocephalus. Therefore this monitoring practice should be performed during the evaluation.


Subject(s)
Humans , Infant, Newborn , Vasoconstriction/drug effects , Hydrocephalus/physiopathology , Mydriatics/administration & dosage , Respiratory Distress Syndrome, Newborn/pathology , Infant, Low Birth Weight , Ductus Arteriosus, Patent/pathology , Mydriatics/adverse effects
6.
Braz. j. med. biol. res ; 50(4): e5520, 2017. graf
Article in English | LILACS | ID: biblio-839279

ABSTRACT

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.


Subject(s)
Animals , Male , Angiotensin I/pharmacology , Antihypertensive Agents/pharmacology , Aorta, Abdominal/drug effects , Coronary Vessels/drug effects , Peptide Fragments/pharmacology , Amlodipine/pharmacology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Blood Pressure/drug effects , Calcium Channel Blockers/pharmacology , Captopril/pharmacology , Losartan/pharmacology , Mineralocorticoid Receptor Antagonists/pharmacology , Models, Animal , Rats, Wistar , Reproducibility of Results , Spironolactone/pharmacology , Time Factors , Vasoconstriction/drug effects , Vasodilation/drug effects
7.
Arq. bras. cardiol ; 107(3): 223-229, Sept. 2016. graf
Article in English | LILACS | ID: lil-796033

ABSTRACT

Abstract Background: Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. Objectives: To determine the effects of jabuticaba hydroalcoholic extract (JHE) on vascular smooth muscle (VSM) of isolated arteries. Methods: Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Results: Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL). Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine) hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM). Conclusion: JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect.


Resumo Fundamentos: Embora a jabuticaba apresente importantes efeitos biológicos, suas ações sobre o sistema cardiovascular ainda não foram esclarecidas. Objetivos: Determinar os efeitos do extrato de jabuticaba (EHJ) sobre o músculo liso vascular (MLV) em artérias isoladas. Métodos: Aortas (sem endotélio) de ratos foram montadas em banho de órgãos isolados para registro de tensão isométrica. Foram verificados o efeito relaxante, a influência dos canais de K+ e das fontes de Ca2+ intra- e extracelular sob a resposta estimulada pelo EHJ. Resultados: Artérias pré-contraídas com fenilefrina apresentaram relaxamento concentração-dependente (0,380 a 1,92 mg/mL). O tratamento com bloqueadores de canais de K+ (tetraetilamônio, glibenclamida, 4-aminopiridina) prejudicaram o relaxamento pelo EHJ. A contração estimulada com fenilefrina também foi prejudicada pelo tratamento prévio com EHJ. A inibição da Ca2+ATPase do reticulo sarcoplasmático não alterou o relaxamento pelo EHJ. Além disso, o EHJ inibiu a contração causada pelo influxo de Ca2+ estimulado por fenilefrina e KCl (75 mM). Conclusão: O EHJ induz vasodilatação independente do endotélio. Ativação dos canais de K+ e inibição do influxo de Ca2+ através da membrana estão envolvidas no efeito relaxante do EHJ.


Subject(s)
Animals , Male , Vasodilator Agents/pharmacology , Plant Extracts/pharmacology , Myrtaceae/chemistry , Muscle, Smooth, Vascular/drug effects , Aorta, Thoracic/drug effects , Time Factors , Vasoconstriction/drug effects , Vasodilation/drug effects , Calcium Channel Blockers/pharmacology , Verapamil/pharmacology , Calcium Channels/drug effects , Potassium Channels/drug effects , Cell Membrane/drug effects , Reproducibility of Results , Rats, Wistar , Potassium Channel Blockers/pharmacology
8.
Bauru; s.n; 2016. 138 p. tab, graf.
Thesis in Portuguese | LILACS, BBO | ID: biblio-881841

ABSTRACT

O presente trabalho teve como objetivo avaliar e comparar a reatividade vascular de agentes vasoconstritores presentes nas soluções anestésicas locais (Adrenalina - vasoconstrição e vasodilatação; Felipressina - vasoconstrição), nas doses de 80, 160, 320, 640 e 1280ng (adrenalina) ou 0,25; 0,5; 1; 2 e 4 x10-3UI (felipressina), em leito arterial mesentérico deratos normotensos, diabéticos, hipertensos renais um-rim, um-clip (1R-1C) e hipertensos1R-1C-diabéticos. E correlacionar tal reatividadecom expressão de RNAm dos receptores 1A e 2- adrenérgicos, V1A para vasopressina e AT1A, AT1Be AT2 para angiotensina II visando verificar se a hipertensão arterial e o diabetes mellitus provocam alteração em modelo indutivo e isogênico. Ratos Wistar pesando 110-160g, foram anestesiados com mistura de quetamina e xilazina (50+10mg/ml/kg de peso), tiveram seu abdômen aberto e receberam um clip de prata com abertura 0,25mm na artéria renal esquerda, removendo-se cirurgicamente o rim direito (ratos 1R-1C). Após 14 dias, receberam injeção subcutânea de estreptozotocina (50 e 60mg/kg de peso) para indução do diabetes mellitus sendo a glicemia testada pela veia caudal previamente aos experimentos (diabéticos). Após 30-42 dias da implantação do clip, todos os grupos foram novamente anestesiados e implantou-se cânula de polietileno (PE-50) na artéria carótida esquerda para registro direto da pressão arterial. Após registro da pressão os animais tiveram a artéria principal mesentérica exposta e canulada. O leito arterial mesentérico foi então isolado e colocado em banho com solução nutritiva de Krebs a 37ºC. O cateter foi conectado ao sistema de registro computadorizado (PowerLab®) utilizando software específico (Chart 5Pro ®). Analisaram-se: a pressão máxima (vasoconstrição) e mínima (vasodilatação), o tempo necessário para atingir esse valor, duração total da resposta, integral e integral sobre a linha de base. Os dados foram submetidos à análise de variância de medidas repetidas (ANOVA), seguida do teste de Holm-Sidak (distribuição normal) ou de Mann-Whitney (nãoparamétrico), quando apropriado, nível de significância de 5%. Todas as respostas máximas de vasoconstrição apresentaram comportamento dose-dependente, contudo, para os quatro grupos estudados, a resposta vasoconstritora para adrenalina foi significativamente superior à felipressina (p<0,05). Diabetes e hipertensão reduziram a resposta vasoconstritora da adrenalina e da felipressina, valores de integral sobre a linha de base, respectivamente para grupo controle, diabético, hipertenso e hipertenso-diabético: 2462±465; 1511±236; 2542± 5456 e 3749±819mmHg.s (p<0,05) para adrenalina e 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0,05) para felipressina. Tanto o diabetes quanto a hipertensão, associadas ou não, aumentaram significativamente o tempo para atingir a pressão máxima de vasoconstrição e a duração (p<0,05). As artérias mesentéricas de ratos diabéticos, hipertensos e diabéticos-hipertensos apresentaram expressão significativamente aumentada dos receptores 1Aadrenérgico, AT1B e AT2 para angiotensina II (p<0,05), enquanto receptor AT1A estava com a expressão aumentada apenas nos grupos diabéticos. A expressão do receptor 1A-adrenérgico é discrepante com os achados funcionais, o que pode ser justificado pela fase crônica da doença em que a PCR foi realizada. É possível correlacionar os dados obtidos com a menor atividade vasoconstritora da felipressina observada clinicamente. A maior sensibilidade às moléculas vasoconstritoras pode explicar a maior tendência de pacientes diabéticos desenvolverem hipertensão. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em pacientes hipertensos e diabéticos, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.(AU)


The main goal of this study wasto evaluate and compare vasoconstrictor agents present in local anesthetic solutions (Epinephrine - vasoconstriction and vasodilation, Felypressin - vasoconstriction) vascular reactivity on mesenteric artery bed of normotensive, diabetic, renal hypertensive one-kidney-one-clip (1K1C) and hypertensive 1K1C diabetic rats. Dosagesstudied were 80, 160, 320, 640 and 1280ng (epinephrine) or 0,25; 0,5;1; 2 and 4 x 10-3UI (felypressin). Also, we aimed to correlate artery response with RNAm expression of 1A and 2-adrenoceptors, V1A vasopressin receptor and AT1A, AT1B e AT2 angiotensin receptors, in order to verify if arterial hypertension and diabetes can lead to alterations on a inductive and isogenic model. Wistar male rats weighing 110-160g were anaesthetized with a mixture of ketamine and xylazine (50+10mg/ml/kg), had their abdominal cavity opened and a silver clipwith 0.25-mm gap was implanted in the main left kidney artery, the right kidney was surgically removed (1K1C-rats). After 14 days, they received a subcutaneous injection of streptozotocin (50 and 60 mg/ml/kg) for inducing diabetes, whereas the glycemia was tested via the tail vein prior to surgery (diabetic rats). Around 30-42 after the clip was implanted, all the groups were anaesthetized again and a polyethylene (PE-50) cannula was implanted on the left carotid artery for direct arterial pressure register. After registering the pressure, the animals had their main mesenteric artery exposed and cannulated. The mesenteric artery bed was then isolated and transferred to a bath with Krebs nutritive solution at 37ºC. The catheter was connected to the computer register system (PowerLab®) using a specific software (Chart 5Pro ®). The following parameters were analyzed: maximum (vasoconstriction) and minimal pressure (vasodilating), the amount of time necessary to achieve this number, total duration of the reaction, integral and integral over baseline. The data was submitted to analysis of variance of repeated measures (ANOVA), followed by a Holm-Sidak (normal distribution) test or Mann Whitney (parametrics) test when suitable, with a significance level of 5%. All maximum vasoconstriction results presented dosage-dependant behavior, however, for the four groups tested, the vasoconstrictive result for epinephrine was significantly superior to felypressin (p<0,05). Diabetes and hypertension significantly reducedepinephrine and felypressin vasoconstrictor responses, integral above baseline, respectively, for control, diabetic, hypertensive and hypertensive-diabetic groups:2462±465; 1511±236; 2542± 5456 e 3749±819 mmHg.s (p<0.05, epinephrine) and 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0.05, felypressin). Both diabetes and hypertension, associated or not, significantly increased time necessary to achieve maximum vasoconstrictor response and its duration (p<0,05). Diabetic, hypertensive and hypertensive-diabetic mesenteric arteries presented 1A-adrenoceptor, AT1B and AT2 angiotensin II-receptor gene expression significantly increased when compared with control group (p<0,05), while AT1Areceptor presented this pattern only in diabetic groups.1A-adrenoceptor gene expression did not confirm functional data, probably due to chronic disease state in wich PCR was performed. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em ratos hipertensos e diabéticos não tratados, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.Its possible to correlate our datawith reducedvasoconstrictor activity of felypressinin clinical use. Increased sensibility and receptor population for vasoconstrictor endogenous molecules could explain diabetic populations tendency to develop arterial hypertension. Our results suggest that epinephrine is more potent than felypressin and both vasoconstrictors presents reduced effects on diabetic and hypertensive patients, what reinforces vasoconstrictor associated with local anesthetic use in this population.(AU)


Subject(s)
Animals , Male , Rats , Anesthetics, Local/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Epinephrine/pharmacology , Felypressin/pharmacology , Hypertension/physiopathology , Mesenteric Arteries/drug effects , Vasoconstrictor Agents/pharmacology , Adrenergic beta-2 Receptor Agonists/analysis , Angiotensin II/analysis , Rats, Wistar , Receptors, Adrenergic, alpha-1/analysis , Time Factors , Vasoconstriction/drug effects , Vasopressins/analysis
9.
Arq. neuropsiquiatr ; 73(2): 119-124, 02/2015. tab
Article in English | LILACS | ID: lil-741172

ABSTRACT

Neurological diseases are common in inflammatory bowel disease (IBD) patients, but their exact prevalence is unknown. Method We prospectively evaluated the presence of neurological disorders in 121 patients with IBD [51 with Crohn's disease (CD) and 70 with ulcerative colitis (UC)] and 50 controls (gastritis and dyspepsia) over 3 years. Results Our standard neurological evaluation (that included electrodiagnostic testing) revealed that CD patients were 7.4 times more likely to develop large-fiber neuropathy than controls (p = 0.045), 7.1 times more likely to develop any type of neuromuscular condition (p = 0.001) and 5.1 times more likely to develop autonomic complaints (p = 0.027). UC patients were 5 times more likely to develop large-fiber neuropathy (p = 0.027) and 3.1 times more likely to develop any type of neuromuscular condition (p = 0.015). Conclusion In summary, this is the first study to prospectively establish that both CD and UC patients are more prone to neuromuscular diseases than patients with gastritis and dyspepsia. .


Doenças neurológicas são comuns em pacientes com doença inflamatória intestinal (DII), mas sua prevalência exata é desconhecida. Métodos Nós estudamos prospectivamente a presença de distúrbios neurológicos em 121 pacientes com DII [51 com doença de Crohn (DC) e 70 com colite ulcerativa (RCU)] e 50 controles (gastrite e dispepsia) ao longo de 3 anos. Resultados A avaliação neurológica padronizada (que incluiu testes eletrodiagnósticos) demonstrou que pacientes com DC foram 7,4 vezes mais propensos a desenvolver neuropatias de fibras grossas do que os controles (p = 0,045), 7,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,001) e 5,1 vezes mais propensos a desenvolver queixas autonômicas (p = 0,027). Pacientes com RCU foram 5 vezes mais propensos de desenvolver neuropatia de fibras grossas (p = 0,027) e 3,1 vezes mais propensos a desenvolver qualquer tipo de condição neuromuscular (p = 0,015). Conclusão Em resumo, este é o primeiro estudo prospectivo a estabelecer que os pacientes tanto com DC quanto de RCU são mais propensos a doenças neuromusculares do que os pacientes com gastrite e dispepsia. .


Subject(s)
Animals , Female , Pregnancy , Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Microcirculation/drug effects , Muscle, Skeletal/blood supply , Prenatal Exposure Delayed Effects , Acetylcholine/pharmacology , Body Weight/drug effects , Bradykinin/pharmacology , Endothelium, Vascular/drug effects , Enzyme Inhibitors/pharmacology , Femoral Artery/drug effects , Femoral Artery/embryology , Microcirculation/embryology , NG-Nitroarginine Methyl Ester/pharmacology , Nitroprusside/pharmacology , Sheep , Vascular Resistance/drug effects , Vasoconstriction/drug effects , Vasodilation/drug effects , Vasodilator Agents/pharmacology
10.
Braz. j. med. biol. res ; 47(10): 826-833, 10/2014. graf
Article in English | LILACS | ID: lil-722174

ABSTRACT

O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca2+/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.


Subject(s)
Animals , Male , Muscle, Smooth, Vascular/physiology , Myosin Light Chains/metabolism , Protein Processing, Post-Translational/physiology , Vasoconstriction/physiology , Aorta, Thoracic , Acetylglucosamine/analogs & derivatives , Acetylglucosamine/pharmacology , Acylation/drug effects , Acylation/physiology , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Azepines/pharmacology , Blotting, Western , Enzyme Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Myosin-Light-Chain Kinase/metabolism , Myosin-Light-Chain Phosphatase/metabolism , Oxazoles/pharmacology , Oximes/pharmacology , Phenylcarbamates/pharmacology , Phenylephrine/agonists , Phosphorylation/drug effects , Phosphorylation/physiology , Rats, Wistar , Ribonucleotides/pharmacology , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , beta-N-Acetylhexosaminidases/antagonists & inhibitors
11.
Braz. j. med. biol. res ; 47(9): 789-798, 09/2014. graf
Article in English | LILACS | ID: lil-719317

ABSTRACT

We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.


Subject(s)
Animals , Male , Aorta, Thoracic/physiopathology , Aortic Coarctation/physiopathology , Calcium/metabolism , Endothelium, Vascular/physiology , Muscle, Smooth, Vascular/physiopathology , Protein Kinase C/antagonists & inhibitors , Vasoconstriction/physiology , Angiotensin I/analysis , Angiotensin II/analysis , Aorta, Thoracic/injuries , Aorta, Thoracic/surgery , Blotting, Western , Blood Pressure/physiology , Chromatography, High Pressure Liquid , Endothelium, Vascular/injuries , Muscle, Smooth, Vascular/metabolism , Neuromuscular Depolarizing Agents/pharmacology , Phenylephrine/pharmacology , Potassium/pharmacology , Protein Kinase C/metabolism , Radioimmunoassay , Rats, Wistar , /metabolism , Vasoconstriction/drug effects
12.
Braz. j. med. biol. res ; 47(5): 411-418, 02/05/2014. tab, graf
Article in English | LILACS | ID: lil-709437

ABSTRACT

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia.


Subject(s)
Adult , Humans , Male , Acetylcholine/pharmacology , Cardiovascular Agents/pharmacology , Hand/blood supply , Nitroprusside/pharmacology , Phenylephrine/pharmacology , Transcutaneous Electric Nerve Stimulation/methods , Analysis of Variance , Blood Glucose , Cholesterol/blood , Erythrocyte Count , Leukocyte Count , Lipoproteins, HDL/blood , Triglycerides/blood , Urea/blood , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Veins/drug effects
13.
Braz. j. med. biol. res ; 47(2): 119-127, 2/2014. graf
Article in English | LILACS | ID: lil-699771

ABSTRACT

Vascular calcification decreases compliance and increases morbidity. Mechanisms of this process are unclear. The role of oxidative stress and effects of antioxidants have been poorly explored. We investigated effects of the antioxidants lipoic acid (LA) and tempol in a model of atherosclerosis associated with elastocalcinosis. Male New Zealand white rabbits (2.5-3.0 kg) were fed regular chow (controls) or a 0.5% cholesterol (chol) diet+104 IU/day vitamin D2 (vitD) for 12 weeks, and assigned to treatment with water (vehicle, n=20), 0.12 mmol·kg-1·day-1 LA (n=11) or 0.1 mmol·kg-1·day-1 tempol (n=15). Chol+vitD-fed rabbits developed atherosclerotic plaques associated with expansive remodeling, elastic fiber disruption, medial calcification, and increased aortic stiffness. Histologically, LA prevented medial calcification by ∼60% and aortic stiffening by ∼60%. LA also preserved responsiveness to constrictor agents, while intima-media thickening was increased. In contrast to LA, tempol was associated with increased plaque collagen content, medial calcification and aortic stiffness, and produced differential changes in vasoactive responses in the chol+vitD group. Both LA and tempol prevented superoxide signals with chol+vitD. However, only LA prevented hydrogen peroxide-related signals with chol+vitD, while tempol enhanced them. These data suggest that LA, opposite to tempol, can minimize calcification and compliance loss in elastocalcionosis by inhibition of hydrogen peroxide generation.


Subject(s)
Animals , Male , Rabbits , Arteriosclerosis/prevention & control , Cyclic N-Oxides/administration & dosage , Thioctic Acid/administration & dosage , Vascular Calcification/prevention & control , Aorta, Thoracic , Arteriosclerosis/chemically induced , Arteriosclerosis/metabolism , Compliance/drug effects , Compliance/physiology , Disease Models, Animal , Spin Labels , Vascular Resistance , Vascular Calcification/chemically induced , Vasoconstriction/drug effects , Vasoconstriction/physiology
14.
Arq. bras. cardiol ; 98(4): 290-299, abr. 2012. ilus, tab
Article in Portuguese | LILACS | ID: lil-639415

ABSTRACT

FUNDAMENTO: Não há consenso sobre o impacto do implante de stent sobre a função endotelial no longo prazo. Há relatos de disfunção endotelial aumentada com stent com sirolimus quando comparado com o stent metálico convencional (BMS). OBJETIVO: Este estudo visa a avaliar o impacto do BMS e o efeito do sirolimus por via oral sobre a função endotelial. MÉTODOS: Quarenta e cinco pacientes foram randomizados em três grupos: BMS + altas doses de sirolimus oral (dose inicial de 15 mg, seguida de 6 mg/dia durante quatro semanas); BMS + baixa dose de sirolimus (6 mg, seguida de 2 mg por dia durante quatro semanas) e BMS sem sirolimus. Mudanças na vasoconstrição ou vasodilatação, em um segmento de 15 milímetros começando pelo extremo distal do stent em resposta a acetilcolina e nitroglicerina, foram avaliadas por angiografia quantitativa. RESULTADOS: Os grupos apresentaram características angiográficas semelhantes. A variação percentual de diâmetro em resposta a acetilcolina foi semelhante em todos os grupos, nos dois momentos (p = 0,469). Quatro horas após o implante de stent, o segmento alvo apresentou uma disfunção endotelial que se manteve após oito meses em todos os grupos. Em todos os grupos, a vasomotricidade independente de endotélio em resposta a nitroglicerina foi semelhante, às quatro horas e aos oito meses, com diâmetro do segmento alvo aumentado após a infusão de nitroglicerina (p = 0,001). CONCLUSÃO: A disfunção endotelial esteve igualmente presente no segmento distal de 15 milímetros do segmento tratado, às 4 horas e aos 8 meses após implante do stent. O sirolimus administrado por via oral durante quatro semanas para evitar a reestenose não afetou o estado de vasomotricidade endotélio dependente e independente.


BACKGROUND: There is no consensus regarding the impact of stenting on long-term endothelial function. There have been reports of increased endothelial dysfunction with sirolimus-eluting stents as compared to bare metal stenting (BMS). OBJECTIVE: This study aims to assess the impact of BMS and the effect of oral sirolimus on endothelial function. METHODS: Forty-five patients were randomized into three groups: BMS + high-dose oral sirolimus (initial dose of 15 mg, followed by 6 mg/day for four weeks); BMS + low-dose sirolimus (6 mg followed by 2 mg daily for four weeks); and BMS without sirolimus. Changes in vasoconstriction or vasodilation in a 15 mm segment starting at the distal stent end in response to acetylcholine and nitroglycerin were assessed by quantitative angiography. RESULTS: The groups had similar angiographic characteristics. The percent variation in diameter in response to acetylcholine was similar in all groups at the two time points (p = 0.469). Four hours after stenting, the target segment presented an endothelial dysfunction that was maintained after eight months in all groups. In all groups, endothelium-independent vasomotion in response to nitroglycerin was similar at four hours and eight months, with increased target segment diameter after nitroglycerin infusion (p = 0.001). CONCLUSION: The endothelial dysfunction was similarly present at the 15 mm segment distal to the treated segment, at 4 hours and 8 months after stenting. Sirolimus administered orally during 4 weeks to prevent restenosis did not affect the status of endothelium-dependent and independent vasomotion.


Subject(s)
Adult , Female , Humans , Middle Aged , Coronary Vessels/drug effects , Endothelium, Vascular/drug effects , Immunosuppressive Agents/pharmacology , Sirolimus/pharmacology , Stents/adverse effects , Vasomotor System/drug effects , Administration, Oral , Analysis of Variance , Acetylcholine/pharmacology , Acetylcholine/therapeutic use , Coronary Vessels/physiopathology , Endothelium, Vascular/physiopathology , Immunosuppressive Agents/administration & dosage , Nitroglycerin/pharmacology , Nitroglycerin/therapeutic use , Sirolimus/administration & dosage , Time Factors , Vasoconstriction/drug effects , Vasoconstriction/physiology , Vasodilation/drug effects , Vasodilation/physiology , Vasodilator Agents/pharmacology , Vasodilator Agents/therapeutic use , Vasomotor System/physiopathology
15.
Experimental & Molecular Medicine ; : 594-602, 2012.
Article in English | WPRIM | ID: wpr-14963

ABSTRACT

The incidence of cardiovascular disease is predicted to increase as the population ages. There is accumulating evidence that arginase upregulation is associated with impaired endothelial function. Here, we demonstrate that arginase II (ArgII) is upregulated in aortic vessels of aged mice and contributes to decreased nitric oxide (NO) generation and increased reactive oxygen species (ROS) production via endothelial nitric oxide synthase (eNOS) uncoupling. Inhibiting ArgII with small interfering RNA technique restored eNOS coupling to that observed in young mice and increased NO generation and decreased ROS production. Furthermore, enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxation responses to acetylcholine in aged vasculature were markedly improved following siRNA treatment against ArgII. These results might be associated with increased L-arginine bioavailability. Collectively, these results suggest that ArgII may be a valuable target in age-dependent vascular diseases.


Subject(s)
Animals , Mice , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Aging , Aorta/enzymology , Arginase/genetics , Endothelium, Vascular/enzymology , Enzyme Induction , Gene Knockdown Techniques , Mice, Inbred C57BL , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , RNA, Small Interfering/genetics , Reactive Oxygen Species/metabolism , Up-Regulation , Vasoconstriction/drug effects
16.
Experimental & Molecular Medicine ; : 749-755, 2012.
Article in English | WPRIM | ID: wpr-110117

ABSTRACT

Cinnamyl alcohol (CAL) is known as an antipyretic, and a recent study showed its vasodilatory activity without explaining the mechanism. Here we demonstrate the vasodilatory effect and the mechanism of action of CAL in rat thoracic aorta. The change of tension in aortic strips treated with CAL was measured in an organ bath system. In addition, vascular strips or human umbilical vein endothelial cells (HUVECs) were used for biochemical experiments such as Western blot and nitrite and cyclic guanosine monophosphate (cGMP) measurements. CAL attenuated the vasoconstriction of phenylephrine (PE, 1 microM)-precontracted aortic strips in an endothelium-dependent manner. CAL-induced vasorelaxation was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME; 10(-4) M), methylene blue (MB; 10(-5) M) and 1 H-[1,2,4]-oxadiazolole-[4,3-a] quinoxalin-10one, (ODQ; 10(-6) or 10(-7) M) in the endothelium-intact aortic strips. Atrial natriuretic peptide (ANP; 10(-8) or 10(-9) M) did not affect the vasodilatory effect of CAL. The phosphorylation of endothelial nitric oxide synthase (eNOS) and generation of nitric oxide (NO) were stimulated by CAL treatment in HUVECs and inhibited by treatment with L-NAME. In addition, cGMP and PKG1 activation in aortic strips treated with CAL were also significantly inhibited by L-NAME. Furthermore, CAL relaxed Rho-kinase activator calpeptin-precontracted aortic strips, and the vasodilatory effect of CAL was inhibited by the ATP-sensitive K+ channel inhibitor glibenclamide (Gli; 10(-5) M) and the voltage-dependent K+ channel inhibitor 4-aminopyridine (4-AP; 2 x 10(-4) M). These results suggest that CAL induces vasorelaxation by activating K+ channels via the NO-cGMP-PKG pathway and the inhibition of Rho-kinase.


Subject(s)
Animals , Humans , Male , Rats , Aorta/drug effects , Atrial Natriuretic Factor/pharmacology , Cyclic GMP/metabolism , Cyclic GMP-Dependent Protein Kinases/metabolism , Dipeptides/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Methylene Blue/pharmacology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Nitric Oxide Synthase/metabolism , Oxadiazoles/pharmacology , Phenylephrine/pharmacology , Phosphorylation , Potassium Channel Blockers/pharmacology , Potassium Channels/agonists , Propanols/pharmacology , Quinoxalines/pharmacology , Rats, Sprague-Dawley , Signal Transduction , Vasoconstriction/drug effects , Vasodilation/drug effects , rho-Associated Kinases/antagonists & inhibitors
17.
Braz. j. med. biol. res ; 44(5): 445-452, May 2011. ilus, tab
Article in English | LILACS | ID: lil-586508

ABSTRACT

Gadolinium (Gd) blocks intra- and extracellular ATP hydrolysis. We determined whether Gd affects vascular reactivity to contractile responses to phenylephrine (PHE) by blocking aortic ectonucleoside triphosphate diphosphohydrolase (E-NTPDase). Wistar rats of both sexes (260-300 g, 23 females, 7 males) were used. Experiments were performed before and after incubation of aortic rings with 3 µM Gd. Concentration-response curves to PHE (0.1 nM to 0.1 mM) were obtained in the presence and absence of endothelium, after incubation with 100 µM L-NAME, 10 µM losartan, or 10 µM enalaprilat. Gd significantly increased the maximum response (control: 72.3 ± 3.5; Gd: 101.3 ± 6.4 percent) and sensitivity (control: 6.6 ± 0.1; Gd: 10.5 ± 2.8 percent) to PHE. To investigate the blockade of E-NTDase activity by Gd, we added 1 mM ATP to the bath. ATP reduced smooth muscle tension and Gd increased its relaxing effect (control: -33.5 ± 4.1; Gd: -47.4 ± 4.1 percent). Endothelial damage abolished the effect of Gd on the contractile responses to PHE (control: 132.6 ± 8.6; Gd: 122.4 ± 7.1 percent). L-NAME + Gd in the presence of endothelium reduced PHE contractile responses (control/L-NAME: 151.1 ± 28.8; L-NAME + Gd: 67.9 ± 19 percent AUC). ATP hydrolysis was reduced after Gd administration, which led to ATP accumulation in the nutrient solution and reduced ADP concentration, while adenosine levels remained the same. Incubation with Gd plus losartan and enalaprilat eliminated the pressor effects of Gd. Gd increased vascular reactivity to PHE regardless of the reduction of E-NTPDase activity and adenosine production. Moreover, the increased reactivity to PHE promoted by Gd was endothelium-dependent, reducing NO bioavailability and involving an increased stimulation of angiotensin-converting enzyme and angiotensin II AT1 receptors.


Subject(s)
Animals , Female , Male , Rats , Aorta/drug effects , Gadolinium/pharmacology , Phenylephrine/pharmacology , Vasoconstriction/drug effects , Vasodilation/drug effects , Antihypertensive Agents/pharmacology , Aorta/physiology , Dose-Response Relationship, Drug , Enalaprilat/pharmacology , Endothelium, Vascular/drug effects , Losartan/pharmacology , NG-Nitroarginine Methyl Ester/pharmacology , Rats, Wistar , Vasoconstriction/physiology , Vasodilation/physiology
18.
Indian J Ophthalmol ; 2011 Jan; 59(1): 51-53
Article in English | IMSEAR | ID: sea-136139

ABSTRACT

A 48-year-old man presented following an episode of sudden onset simultaneous inferior altitudinal visual loss in his left eye and visual obscuration with shimmering in the inferonasal quadrant of the right eye. Clinical examination demonstrated left superior hemiretinal artery occlusion and an area of focal dynamic spasm along the right superior temporal branch retinal artery, the arteriolar spastic cycle was about 2 sec in duration. Hematological (including complete blood count, thrombophilia screen, vasculitic screen and serum magnesium), carotid, and cardiac investigations were normal. He was given acetazolamide 500 mg orally, timolol maleate 0.5% eye drops once daily and sublingual amyl-nitrate 0.8 mg, and maintained on felodipine 10 mg/day and aspirin 100 mg/day. The area of focal arteriolar spasm in the right eye resolved over two months. To our knowledge there are no prior reports of photographically documented dynamic focal retinal vascular spasm on a MEDLINE and PUBMED search.


Subject(s)
Arterioles/drug effects , Arterioles/pathology , Drug Administration Schedule , Follow-Up Studies , Fundus Oculi , Humans , Male , Middle Aged , Migraine Disorders/complications , Migraine Disorders/physiopathology , Photography , Retinal Artery Occlusion/etiology , Retinal Artery Occlusion/pathology , Retinal Vessels/drug effects , Retinal Vessels/pathology , Vasoconstriction/drug effects , Vasodilator Agents/administration & dosage
19.
Clinics ; 66(12): 2125-2132, 2011. graf
Article in English | LILACS | ID: lil-609012

ABSTRACT

OBJECTIVES: The goal of this study was to determine the possible mechanism that is involved in the blood pressureraising effect of heated vegetable oils. METHODS: Adult male Sprague-Dawley rats were divided into 11 groups; the control group was fed with rat chow, and the other groups were fed with chow that was mixed with 15 percent weight/weight palm or soy oils, which were either in a fresh form or heated once, twice, five, or ten times. Blood pressures were measured at the baseline and throughout the 24-week study. Plasma nitric oxide levels were assessed prior to treatment and at the end of the study. Following 24 weeks, the rats were sacrificed to investigate their vascular reactivity using the thoracic aorta. RESULTS: Palm and soy oils had no detrimental effects on blood pressure, and they significantly elevated the nitric oxide contents and reduced the contractile responses to phenylephrine. However, trials using palm and soy oils that were repeatedly heated showed an increase in blood pressure, enhanced phenylephrine-induced contractions, reduced acetylcholine- and sodium nitroprusside-induced relaxations relative to the control and rats that were fed fresh vegetable oils. CONCLUSIONS: The blood pressure-raising effect of the heated vegetable cooking oils is associated with increased vascular reactivity and a reduction in nitric oxide levels. The chronic consumption of heated vegetable oils leads to disturbances in endogenous vascular regulatory substances, such as nitric oxide. The thermal oxidation of the cooking oils promotes the generation of free radicals and may play an important contributory role in the pathogenesis of hypertension in rats.


Subject(s)
Animals , Male , Rats , Aorta, Thoracic/drug effects , Blood Pressure/drug effects , Endothelium, Vascular/drug effects , Hot Temperature , Plant Oils/pharmacology , Soybean Oil/pharmacology , Acetylcholine/pharmacology , Aorta, Thoracic/physiology , Endothelium, Vascular/physiology , Nitric Oxide/analysis , Nitroprusside/pharmacology , Rats, Sprague-Dawley , Vasoconstriction/drug effects , Vasodilation/drug effects
20.
Journal of Forensic Medicine ; (6): 81-90, 2011.
Article in Chinese | WPRIM | ID: wpr-983628

ABSTRACT

OBJECTIVE@#To observe the effect of soft tissue crush injury on the tensions of thoracic aortic rings (TARs) in rats and to investigate the potential roles of nitric oxide in the change of the tensions.@*METHODS@#Thirty adult SD rats were randomly divided into control group and crush injury (8 h and 16 h after injury) groups. Two kinds of TARs (one with endothelium and the other without endothelium) in vitro were prepared. In the TARs with endothelium, the tensions induced by phenylephrine (PE), acetylcholine (Ach), calcium ionophore A23187 and angiotensin II (AngI) were measured by the vascular tension detective technique. Then the TARs with endothelium were preincubated with nitric oxide synthase inhibitor N-nitro-L-arginine (L-NNA) for 20 minutes, the tensions induced by PE and Ang II were measured again. In the TARs without endothelium, the tensions induced by PE and Ang II were measured by the same method.@*RESULTS@#In the TARs with endothelium, the tension of relaxation induced by cumulative doses of Ach and A23187 decreased significantly in 8 h and 16h groups. The tension of contraction induced by cumulative doses of PE and Ang II also decreased significantly (P<0.05). The tension of contraction increased after the preincubation with L-NNA. In the TARs without endothelium, the tension of contraction induced by PE and Ang II increased comparing to that of TARs with endothelium.@*CONCLUSION@#The soft tissue crush injury can influence the tensions of TARs in rats and the vascular-derived NO can mediate the effects.


Subject(s)
Animals , Female , Male , Rats , Aorta, Thoracic/physiopathology , Disease Models, Animal , Endothelium, Vascular/metabolism , Hindlimb/injuries , Muscle, Smooth, Vascular/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/metabolism , Random Allocation , Rats, Sprague-Dawley , Soft Tissue Injuries/physiopathology , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology
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