Canales de iones potasio en la dinámica contráctil del músculo liso arterial inducida por Camphenol Plus

RESUMEN Introducción: El Camphenol Plus es un derivado clorofenólico empleado como medicación intraconducto durante los tratamientos pulporradiculares en Estomatología. Son escasos los reportes científicos sobre el papel de los canales de iones potasio en la dinámica contráctil del músculo liso arterial inducida por dicho medicamento. Objetivo: Determinar el papel de los canales de iones potasio en la dinámica contráctil del músculo liso arterial inducida por Camphenol Plus. Método: Se realizó una investigación experimental preclínica en el Instituto de Fisiología "Oscar Langerdorff", Facultad de Medicina, Universidad de Rostock, Alemania, entre octubre y diciembre de 2018, con el empleo de 30 anillos de aorta obtenidos de 10 ratas Wistar (n=10). Las preparaciones biológicas se colocaron en baño de órganos y se preactivaron con solución Krebs concentrada en iones potasio, registrándose luego la tensión desarrollada por el músculo liso vascular tras la adición de soluciones de Camphenol Plus durante diferentes intervalos de tiempo. Se utilizaron las pruebas de Wilcoxon y U de Mann-Whitney. Resultados: El 31,4 % de la musculatura lisa vascular se relajó por acción del Camphenol Plus tras la preactivación con solución Krebs concentrada en iones potasio. El mayor descenso del tono vascular se produjo con el uso de soluciones del medicamento al 7 % entre el primer y tercer minutos. Conclusiones : El efecto vasorrelajante in vitro producido por Camphenol Plus sobre el músculo liso arterial está mediado por canales de iones potasio sensibles a voltaje, a calcio y a trifosfato de adenosina del endotelio vascular y el sarcolema.

ABSTRACT Introduction: Camphenol Plus is a chlorophenolic derivative commonly used as an intra - duct medication for pulporadicular treatments in Dentistry. Scientific reports about the use of this medication on the role of potassium ion channels in the contractile dynamics of induced arterial smooth muscle are low. Objective: To determine the role of potassium ion channels in the contractile dynamics of Camphenol Plus - induced arterial smooth muscle. Method: A preclinical experimental investigation was performed at the "Oscar Langerdorff" Institute of Physiology, Rostock University Medical Center, Rostock, Germany, between October and December 2018. A total of 30 aortic rings obtained from 10 Wistar rats (n=10) were used. The biological preparations were placed in an organ bath and preactivated with Krebs solution concentrated in potassium ions, afterwards it was recorded the tension developed by the vascular smooth muscle after applying the Camphenol Plus solutions in different time intervals. The Mann-Whitney U test and Wilcoxon test were applied. Results: The 31.4% of vascular smooth muscle was relaxed by the effect of Camphenol Plus after preactivation with Krebs solution concentrated in potassium ions. The greatest decrease in vascular tone occurred between the first and third minutes after the use of the drug solutions prepared at 7 %. Conclusions: The in vitro vasorelaxant effect produced by the Camphenol Plus medication on arterial smooth muscle is mediated by the potassium ion channels sensitive to voltage, calcium and the adenosine triphosphate of the vascular endothelium and sarcolemma.

RESUMO Introdução: Camphenol Plus é um derivado clorofenólico utilizado como medicação intracanal durante tratamentos pulporradiculares em Estomatologia. Existem poucos relatos científicos sobre o papel dos canais iônicos de potássio na dinâmica contrátil do músculo liso arterial induzida pela referida droga. Objetivo: Determinar o papel dos canais iônicos de potássio na dinâmica contrátil do músculo liso arterial induzida por Camphenol Plus. Método: Uma investigação experimental pré-clínica foi realizada no Instituto de Fisiologia "Oscar Langerdorff" da Faculdade de Medicina da Universidade de Rostock, Alemanha, entre outubro e dezembro de 2018, utilizando 30 anéis aórticos obtidos de 10 ratos Wistar (n=10). As preparações biológicas foram colocadas em banho de órgãos e pré-ativadas com solução de Krebs concentrada em íons potássio, registrando-se então a tensão desenvolvida pelo músculo liso vascular após a adição de soluções de Camphenol Plus em diferentes intervalos de tempo. Foram utilizados os testes U de Wilcoxon e Mann-Whitney. Resultados: 31,4% da musculatura lisa vascular relaxada pela ação do Camphenol Plus após pré-ativação com solução de Krebs concentrada em íons potássio. A maior diminuição do tônus vascular ocorreu com o uso de soluções medicamentosas a 7% entre o primeiro e o terceiro minutos. Conclusões: O efeito vasorrelaxante in vitro produzido pelo Camphenol Plus no músculo liso arterial é mediado por canais de íons de potássio sensíveis à voltagem, trifosfato de cálcio e adenosina do endotélio vascular e do sarcolema.

Global endothelial function assessment using pulse wave analysis in hypercholesterolemia

To compare global endothelial function assessed by pulse wave analysis (PWA) using the ratio of endothelium dependent vasodilatation (EDV) to endothelium independent vasodilatation (EIV) in patients with hypercholesterolemia and controls. 92 subjects [46 hypercholesterolemics, 46 controls] were studied at standardized conditions. Baseline augmentation index (AIx) was assessed followed by the administration of 0.5 mg sublingual nitroglycerine, an endothelium independent vasodilator. AIx was assessed and the maximum change in AIx after nitroglycerine was recorded as EIV. After a washout period of 30 minutes, 400 µg of inhaled salbutamol, an endothelium dependent vasodilator was administered. AIx was assessed again and the maximum change in AIx after salbutamol was recorded as EDV. Global endothelial function was calculated as EDV:EIV ratio. EDV and EIV in patients with hypercholesterolemia compared to controls were 2.97 ± 3.95 and 6.65 ± 3.80 (p<0.001); and 13.41 ± 4.57 and 15.88 ± 4.78 (p=0.01) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls; 0.21 ± 0.38 and 0.44 ± 0.24 (p<0.001) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls. PWA is a potential clinical tool to assess global endothelial function in patients with hypercholesterole

O Efeito Anti-Hipertensivo de Sauromatum Guttatum Mediado por Efeitos Vasorrelaxante e Depressivos Miocárdicos / Antihypertensive Activity of Sauromatum guttatum Mediated by Vasorelaxation and Myocardial Depressant Effects

Resumo Fundamento: A Sauromatum guttatum (S. guttatum) é utilizado no tratamento de doenças do sangue e supostamente tem atividade espasmolítica através da inibição dos canais de Ca2+. Objetivos: O objetivo deste estudo foi investigar o potencial anti-hipertensivo de S. guttatum em modelo de rato Sprague-Dawley (SD) com hipertensão induzida por dieta com alto teor de sal (HIDATS). Métodos: Ratos SD foram divididos em normotensos, hipertensos e grupos tratados com verapamil e S. guttatum. Extrato bruto de S. guttatum (Sg.B) (100, 150 e 300 mg/kg/dia) e verapamil (5, 10 e 15 mg/kg/dia) foram administrados por via oral junto com NaCl. Anéis aórticos e faixas do átrio direito de ratos normotensos foram utilizados para investigar os mecanismos subjacentes. O nível de significância estatística adotado foi de 5%. Resultados: A pressão arterial média diminuiu nos grupos hipertensos tratados com Sg.B e verapamil de forma dose-dependente (p <0,001). No estudo de reatividade vascular, a acetilcolina induziu relaxamentos com valor CE50 de 0,6 µg/mL (0,3-1,0) em ratos hipertensos tratados com Sg.B (300 mg/kg), sugerindo preservação endotelial. Em aorta isolada de rato normotenso, o Sg.B exibiu vasorrelaxamento com valor de CE50 de 0,15 mg/mL (0,10-0,20), após ablação por desnudamento endotelial ou pré-tratamento com L-NAME e atropina. O tratamento com Sg.B causou relaxamento contra contrações induzidas por K+ alto, como o verapamil. O Sg.B mostrou efeitos inotrópicos (82%) e cronotrópicos (56%) negativos em preparações isoladas atriais de ratos reduzidas com atropina. A avaliação fitoquímica indicou a presença de alcaloides, flavonoides e taninos. Conclusão: O S. guttatum possui efeito vasodilatador através da preservação da função endotelial, liberação de NO mediada pelo receptor muscarínico e inibição do movimento de Ca2+, enquanto o efeito depressor do miocárdio atrial pode estar ligado ao receptor muscarínico. Esses achados fornecem a base farmacológica para o uso do extrato de S. guttatum como um medicamento anti-hipertensivo.

Abstract Background: Sauromatum guttatum (S. guttatum) is used in the treatment of blood disorders and reportedly has a spasmolytic activity through Ca2+ channel inhibition. Objectives: The aim of this study was to investigate the antihypertensive potential of S. guttatum in high salt-induced hypertensive Sprague-Dawley (SD) rat model (HSHRs). Methods: SD rats were divided into normotensive, hypertensive, S. guttatum and verapamil treated groups. S. guttatum crude extract (Sg.Cr) (100, 150 and 300 mg/kg/day) and verapamil (5, 10 and 15 mg/kg/day) were administered orally along with NaCl. Aortic rings and right atrial strips from normotensive rats were used to investigate the underlying mechanisms. The level of statistical significance was set at 5%. Results: Mean arterial pressure decreased in the Sg.Cr and verapamil-treated hypertensive groups in a dose-dependent manner (p < 0.001). In the vascular reactivity study, acetylcholine induced relaxations with an EC50 value of 0.6 µg/mL (0.3-1.0) in Sg.Cr-treated hypertensive rats (300 mg/kg), suggesting endothelial preservation. In isolated normotensive rat aorta, Sg.Cr-treated rats showed vasorelaxation with an EC50 value of 0.15 mg/mL (0.10-0.20), ablated by endothelial denudation or pretreatment with L-NAME and atropine. Sg.Cr treatment caused relaxation against high K+-induced contractions, like verapamil. Sg.Cr showed negative inotropic (82%) and chronotropic effects (56%) in isolated rat atrial preparations reduced with atropine. The phytochemical investigation indicated presence of alkaloids, flavonoids and tannins. Conclusion: S. guttatum has a vasodilatory effect through endothelial function preservation, muscarinic receptor-mediated NO release and Ca2+ movement inhibition, while atrial myocardial depressant effect can be linked to the muscarinic receptor. These findings provide pharmacological base for using S. guttatum extract as an antihypertensive medication.

Dinámica contráctil inducida por p-clorofenol alcanforado en anillos aórticos de ratas Wistar / Dinâmica contrátil induzida por cânfora-clorofenol em anéis aórticos de ratos Wistar / Camphorated p-chlorophenol-induced contractile dynamics in aortic rings of Wistar rats

Introducción: El p-clorofenol alcanforado es un derivado clorofenólico de uso común como medicación intraconducto en Endodoncia. Son escasos los reportes científicos sobre sus efectos en la musculatura lisa vascular arterial y la regulación del flujo sanguíneo local. Objetivo: Determinar el efecto del p-clorofenol alcanforado sobre la dinámica contráctil del músculo liso vascular arterial en el tiempo. Método: Se realizó una investigación experimental preclínica utilizando 14 anillos de aorta obtenidos de ratas Wistar. Los anillos se colocaron en baño de órganos y se preactivaron con noradrenalina, registrándose luego la tensión desarrollada por el músculo liso vascular tras la adición de p-clorofenol alcanforado durante diferentes intervalos de tiempo. Resultados: El 51,4 porciento de la musculatura lisa vascular se relajó por la acción del p-clorofenol alcanforado. El mayor descenso del tono vascular se produjo entre el tercer y quinto minuto de añadido el medicamento. Las pruebas de Wilcoxon de los rangos con signos evidenciaron diferencias significativas entre la tensión base inicial y la registrada en los diferentes intervalos de tiempo estudiados. Conclusiones: el p-clorofenol alcanforado, induce in vitro, relajación del músculo liso arterial a través de un acoplamiento excitación-contracción de tipo farmacomecánico, la cual se incrementa en función del tiempo(AU).

Introduction: Camphorated p-chlorophenol is a chlorophenolic derivative commonly used as an intra-oral medication in endodontics. Scientific reports on its effects in arterial vascular smooth muscle and local blood flow regulation are scarce. Objective: To determine the effect of camphorated p-chlorophenol on the contractile dynamics of arterial vascular smooth muscle. Method: An experimental and preclinical research was conducted with the use of 14 aortic rings of Wistar rats. The rings were placed in an organ bath and preactivated with noradrenaline, and the tension developed by the vascular smooth muscle at different time intervals was recorded after induction of camphorated p-chlorophenol. Results: Most of the vascular smooth muscle (51.4 percent) relaxed with the use of camphorated p-chlorophenol. The greatest decrease in vascular tone occurred between the third and fifth minute after use the drug. Wilcoxon rank tests showed significant differences between tension observed at baseline and those recorded at the different time intervals studied. Conclusions: Camphorated p-chlorophenol, induces in vitro, relax the arterial smooth muscle through a pharmacomechanical excitation-contraction link, which increases according to the time(AU).

Introdução: O cânfora-clorofenol é um derivado clorofenólico comumente utilizado como medicamento intracanal em Endodontia. Relatórios científicos sobre seus efeitos no músculo liso vascular arterial e na regulação do fluxo sanguíneo local são escassos. Objetivo: Determinar o efeito da cânfora-clorofenol na dinâmica contrátil do músculo liso vascular arterial ao longo do tempo. Método: Foi realizada investigação experimental pré-clínica com 14 anéis aórticos obtidos de ratos Wistar. Os anéis foram colocados em banho de órgãos e pré-ativados com norepinefrina, em seguida, a tensão desenvolvida pela musculatura lisa vascular foi registrada após a adição de cânfora-clorofenol em diferentes intervalos de tempo. Resultados: 51,4 porcento dos músculos lisos vasculares estavam relaxados pela ação do cânfora-clorofenol. A maior diminuição do tônus vascular ocorreu entre o terceiro e o quinto minuto após a adição do medicamento. Os testes de Wilcoxon das faixas com sinais mostraram diferenças significativas entre a tensão base inicial e a registrada nos diferentes intervalos de tempo estudados. Conclusões: O cânfora-clorofenol induz, in vitro, relaxamento da musculatura lisa arterial por meio de um acoplamento excitação-contração do tipo farmacomecânico, que aumenta em função do tempo(AU).

A Study on Usefulness of Flow Mediated Vasodilatation of Brachial Artery in Assessing the Severity of Coronary Artery Disease and its Correlation with Coronary Angiogram

Introduction: The endothelium is a special tissue that releasesnumerous substance that moderates tone of the vascular bed,growth of cells, platelet and WBC interactions. Significantly,the evolution of atherosclerosis occurs much early in life, andendothelial dysfunction accelerates atherosclerosis and occursmuch before the development of morphological changes inthe vascular bed. Hence; the present study was undertakenfor assessing the usefulness of flow mediated vasodilatationof brachial artery in assessing the severity of coronary arterydisease and its correlation with coronary angiogram.Material and methods: A total of 75 subjects were enrolled.Group A included 18 subjects with non-critical CAD, Group Bincluded 33 subjects with SVD, Group C included 8 subjectswith DVD and Group D included 16 subjects with TVD.Complete demographic and clinical details were obtained.All patients who have been diagnosed having coronary arterydisease which includes chronic stable angina, ST elevation MI,non ST elevation MI, unstable angina within the last 1monthand have undergone CAG. Patients were subjected to symptomanalysis, clinical examination, laboratory investigations andflow mediated vasodilation studies of brachial artery. All theresults were analysed by SPSS software.Results: By conventional criteria the association between thestudy groups and smoking is considered to be not statisticallysignificant since p > 0.05. There was meaningfully realincrease in severity of CAD as duration of smoking increasesin our study subjects. By conventional criteria the associationbetween the study groups and alcoholism is considered tobe not statistically significant since p > 0.05. The diabeticstatus in non-critical CAD group is meaningfully less thanDVD group by 1.15 times with a mean difference of 8percentage points. By conventional criteria the associationbetween the study groups and brachial artery resting diameterstatus is considered to be not statistically significant sincep > 0.05. There was meaningfully real increase in severityof CAD as Increase in FMD % decreases in our studysubjects.Conclusion: Apart from assessing the traditionalcardiovascular risk factors, it is also important to assessthe endothelial function of the patient by methods likeFMD.

Acute effects of strength exercise with blood flow restriction on the arterial resistance index / Efeitos agudos do exercício de força com restrição do fluxo sanguíneo sobre o índice de resistência arterial

ABSTRACT The present study aimed to evaluate the acute behavior of the brachial artery resistance index (BARI) and popliteal artery resistance index (PARI) in response to low intensity strength exercises involving small (SMG) and large muscle groups (LMG) performed with and without blood flow restriction. Eleven men (age 23 ± 3.29 years) underwent a four-arm, randomized, cross-over experiment: Small muscle group exercise (SMG), small muscle groups with blood flow restriction (SMG+BFR), large muscle groups (LMG) and large muscle groups with blood flow restriction (LMG+BFR). The behavior of BARI and PARI was evaluated at rest, immediately after exercise, and at 15 and 30 minutes during recovery. Data analysis showed a significant reduction of the BARI from rest to post-exercise only in the protocols involving SMG, regardless of the BFR (p <0.05). Protocols involving LMG, with or without BFR, did not affect PARI (p> 0.05), but were efficient to promote significant increases in BARI (p <0.05) immediately after exercise. Our findings indicate that the exercises involving SMG, regardless of BFR, are efficient to promote local vasodilatation (brachial artery), but without systemic effects. None of the analyzed protocols affected the PARI behavior.

RESUMO O presente estudo objetivou avaliar o comportamento agudo do índice de resistência da artéria braquial (IRAB) e da artéria poplítea (IRAP) em resposta a exercícios de força de baixa intensidade envolvendo pequenos (PGM) e grandes grupos musculares (GGM), realizado com e sem restrição de fluxo sanguíneo. Onze homens (idade 23 ± 3,29 anos) realizaram um experimento randomizado, cruzado, com quatro braços: Exercício para pequenos grupos musculares (PGM), pequenos grupos musculares com restrição de fluxo sanguíneo (PGM+RFS), grandes grupos musculares (GGM) e grandes grupos musculares com restrição de fluxo sanguíneo (GGM+RFS). O comportamento de IRAB e IRAP foi avaliado em repouso, mediatamente após o exercício, e aos 15 e 30 minutos da recuperação. A análise dos dados mostrou uma redução significativa do IRAB do repouso para o pós-exercício apenas nos protocolos de PGM com ou sem RFS (p <0,05). Protocolos envolvendo GGM, independentemente do BFR, não afetaram o IRAP (p> 0,05), porém, foram eficientes para promover aumentos significativos do IRAB (p <0,05) imediatamente após o exercício. Nossos achados indicam que os exercícios envolvendo PGM, independentemente da BFR, são capazes de promover a vasodilatação local (artéria braquial), porém, sem efeitos sistêmicos. Nenhum dos protocolos analisados afetou o comportamento do IRAP.

Discovery of phthalides with vasodilating activity in stems and leaves of Ligusticum chuanxiong / 中草药

Objective: To study the phthalides with vasodilating activity of alcohol extracts from stems and leaves of Ligusticum chuanxiong. Methods: Compounds were isolated by extensive chromatographic techniques including MCI, silica gel, Sephadex LH-20, ODS, and semi-preparative HPLC. The vasodilating effect of phthalide and dimer phthalide on thoracic aortic ring in vitro was investigated. Results: Ten phthalides were isolated and identified, and their structures were elucidated as Z-3-butylidenephthalide (1), senkyunolide-E (2), Z-senkyunolide-H (3), (3Z,7β)-3-butenyl-7-hydroxy-4,5,6,7-tetrahydrophthalide (4), neoligustilide (5); Z,Z’-3.3’a,7.7’a-diligustilide (6), 3Z,3Z’-6,8’,7,3’-diligustilide (7), Z-tokinolide A (8), (3’Z)-(3S,8R,3a’S,6’R)-4,5-dehydro-3.3’a,8.6’-diligustilide (9), and (3Z)-(3aR,6S,3’R,8’S)-3a.8’,6.3’-diligustilide (10). Compound 1, 6-9 significantly reduced the strain of thoracic aortic ring in KCl preconstricted rats. The diastolic rate of compounds 6-8 were 60%, 52% and 70% at the highest concentrations (12 μmol/L), respectively. The EC50 was 9.46, 11.86 and 8.73 μmol/L, respectively. Firstly isolated from the stems and leaves of L. chuanxiong. Compounds 6, 8 are firstly isolated from L. chuanxiong. The test compounds could dilate blood vessels, and the activity of dimer phthalide was better than that of phthalide.

Application of microvascular measurement technology in endothelial removal / 中国药理学通报

Aim To improve the reliability of research data of microvascular measurement technology by establishing a research method for the removal of vascular endothelium from isolated arterioles. Methods For this study, 12-wk-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto ( WKY) rats were selected. Acute separation of the mesenteric artery was performed after measurement of blood pressure. The endothelium was removed by a combination of mechanical (the vascular ring rotated around the electrode tip and gas was injected) and drug (L-NAME and indom-ethacin). Thenthe effects of different concentrations of phenylephrine ( PE), ACh, and sodium nitroprusside (SNP) on the changes of the mesenteric artery diameter in the rats with endothelial integrity and endothelial removal were measured using pressure myocardio-graphy. Results (1) The blood pressure ofSHR rats was significantly higher than that of WKY rats (P could relax the mesenteric artery of SHR and WKY rats in a concentration-dependent manner. When the endothelium was intact, the relaxation of SHR was significantly weaker than that of WKY rats (P < 0. 01 )j Compared with WKY rats, SHR showed a significantly enhanced relaxation when the endothelium was removed (P <0. 01). Conclusions (1) We successfully established a research method for vascular endothelium removal by in vitro arteriolar pressure arthrography. ( 2 ) Hypertensive rats have a significant vasomotor dysfunction.

Evaluation of Myocardial Perfusion by Computed Tomography - Principles, Technical Background and Recommendations / Avaliação da Perfusão Miocárdica por Tomografia Computadorizada - Princípios, Fundamentação Técnica e Recomendações

Abstract Coronary computed tomography angiography (CCTA) has gained a prominent role in the evaluation of coronary artery disease. However, its anatomical nature does not allow the evaluation of the functional repercussion of coronary obstructions. It has been made possible to evaluate Myocardial computed tomography perfusion (Myocardial CTP) recently, based on myocardial contrast changes related to coronary stenoses. Several studies have validated this technique against the anatomical reference method (cardiac catheterization) and other functional methods, including myocardial perfusion scintigraphy and fractional flow reserve. The Myocardial CTP is performed in conjunction with the CCTA, a combined analysis of anatomy and function. The stress phase (with assessment of myocardial perfusion) can be performed before or after the resting phase (assessment of resting perfusion and coronary arteries), and different acquisition parameters are proposed according to the protocol and type of equipment used. Stressors used are based on coronary vasodilation (e.g. dipyridamole, adenosine). Image interpretation, similar to other perfusion assessment methods, is based on the identification and quantification of myocardial perfusion defects. The integration of both perfusion and anatomical findings is fundamental for the examination interpretation algorithm, allowing to define if the stenoses identified are hemodynamically significant and may be related to myocardial ischemia.

Resumo A angiografia coronariana por tomografia computadorizada (ACTC) assumiu um papel de destaque na avaliação da doença arterial coronariana. Entretanto, sua natureza anatômica não permitia a avaliação da repercussão funcional das obstruções coronarianas. Recentemente, tornou-se possível a avaliação da perfusão miocárdica por tomografia computadorizada (PMTC), baseando-se nas alterações de contrastação miocárdicas relacionadas às estenoses coronarianas. Diversos estudos permitiram validar esta técnica perante o método anatômico de referência (cateterismo cardíaco) e outros métodos funcionais, incluindo cintilografia de perfusão miocárdica e a reserva de fluxo fracionada. A PMTC é realizada conjuntamente com a ACTC, em uma análise combinada de anatomia e função. A fase de estresse (com avaliação da perfusão miocárdica) pode ser realizada antes ou depois da fase de repouso (avaliação da perfusão de repouso e artérias coronárias), e diferentes parâmetros de aquisição são propostos conforme o protocolo e o tipo de equipamento utilizados. Os agentes estressores utilizados baseiam-se na vasodilatação coronariana (ex: dipiridamol, adenosina). A interpretação das imagens, semelhante a outros métodos de avaliação perfusional, baseia-se na identificação e quantificação de defeitos de perfusão miocárdicos. A integração dos achados perfusionais e anatômicos é parte fundamental do algoritmo de interpretação do exame, permitindo definir se as estenoses identificadas são hemodinamicamente significativas, podendo se relacionar com isquemia miocárdica.

Antioxidant and Vasodilatory Action of Grape Juices Produced in Different Regions of Brazil

Grapes and its derivatives (wines and juices) are rich in polyphenols that have high antioxidant and vasodilator capacity. These biological activities may vary in the juices marketed and produced in different regions of Brazil. Objectives: To determine the antioxidant and vasorelaxant effects of grape juice samples produced in different regions of Brazil. Methods: The content of phenolic compounds and antioxidant capacity were evaluated by the methods of Folin-Ciocalteau, DPPH, ABTS and a new electroanalytical approach (differential pulse voltammetry - DPV). Vasodilator effects were analyzed in isolated aorta from rats in an organ bath. Results: The samples from RJ and SP presented respectively the higher and lower phenolic content and also antioxidant capacity by the methods used (ABTS and DPPH). The results of the electrochemical index corroborate to the other tests, with the best results to RJ (21.69 ± 3.15 µA/V) and worse to the SP sample (11.30 ± 0.52 µA/V). In the vascular reactivity studies, the relaxation induced by each sample presented more distinct differences, following the order: RJ (87.9 ± 4.8%) > RS1 (71.6 ± 8.6%) > GO (56.2 ± 7.2%) > SP (39.9 ± 7.8%) > PR (39.4 ± 9.5%) > RS2 (19.5 ± 6.2%). Inhibition of endothelial NO practically abolished (p < 0.001) the relaxation for all samples, except one. Conclusion: The phenolic content and antioxidant capacity vary greatly among samples. The results obtained for the order of antioxidant activity were: RJ > RS1 > GO > RS2 > PR > SP. The juices were able to induce vascular relaxation at quite varied levels, and the RJ sample the most effective. The L-NAME practically blocked all samples except one (RS2)

Prevalence of endothelial dysfunction in acquired immune deficiency syndrome patients and its correlation with degree of immunodeficiency

Background: Number of factors play a role in endothelial dysfunction observed in AIDS patients, which can lead to atherosclerosis along with cardiovascular mortality and morbidity. Human immunodeficiency virus (HIV), the etiologic agent of AIDS causes several vascular disorders characterized by an evident activation and perturbation of endothelial cells. Currently, there is lack of data in the Indian literature regarding study of endothelial dysfunction in HIV patients. The purpose of our research was to study the prevalence of endothelial dysfunction in HIV/AIDS patients.Methods: The study comprises a total number of 60 adult HIV positive patients of both sex (male and female) with confirmed HIV seropositivity. The patients were divided into two groups of 30 each, depending on the degree of immune dysfunction (CD 4 cell counts). Group I- patients with CD 4+T cell count>200/µl and group II-patients with CD 4+T cell count<200/µl. These patients were subjected to detailed clinical examination and markers of endothelial dysfunction-flow mediated vasodilatation (FMD) of brachial artery, S. nitrite and C-reactive protein (CRP) were performed.Results: The defect in endothelial function was most prevalent in patients with more severe immunosuppression. FMD of brachial artery was decreased in patients with CD 4+T cell count < 200/µl (7.07±2.89, p=0.00). S. nitrite was also significantly lower in group II patients (26.43±15.38), and these patients also showed more CRP positivity and higher CRP titres ranging from 1.2 mg/dl to 9.6 mg/dl.Conclusions: The defect in endothelial function was most prevalent in patients with more severe immunosuppression. FMD of brachial artery was decreased in patients with CD 4+T cell count <200/µl (7.07±2.89, p=0.00). S. nitrite was also significantly lower in group II patients (26.43±15.38), and these patients also showed more CRP positivity and higher CRP titres ranging from 1.2 mg/dl to 9.6 mg/dl.

The alterations of microvasculature, tyrosine phosphorylation, and lipid peroxidation in kidney of rats treated with valproic acid / Alteraciones de la microvasculatura, fosforilación de tirosina y peroxidación lipídica en riñones de ratas tratadas con ácido valproico

SUMMARY: Valproic acid (VPA), an antiepileptic drug, has been demonstrated to damage histology and to change tyrosine phosphorylation patterns with increased oxidative stress in perirenal tissues. This study aimed to investigate the effect of VPA on microstructure, tyrosine phosphorylation, and lipid peroxidation of rat kidney. Adult male rats were divided into control and VPA-treated groups intraperitoneally injected with normal saline and VPA 500 mg/kgBW for 10 consecutive days, respectively (n = 7 each). The blood serum was examined for biochemical levels. The kidney tissues were routinely processed for histological observation. Total proteins from kidney were extracted to assay the malondialdehyde (MDA) levels and phosphorylation expression. The results showed that VPA significantly decreased blood glucose levels while tend to increase urea nitrogen and creatinine. MDA levels in VPA group were significantly higher that of control. Renal cortex of VPA-treated animals revealed vasodilatations. Although the ratio of a renal phosphorylated 72 kDa protein/ beta actin expression seemed to be not different in both groups, VPA significantly decreased the intensity of beta actin. In conclusion, VPA dilates renal microvasculature with increasing of MDA but suppresses the actin expression.

RESUMEN: Se ha demostrado que el ácido valproico (AVP), un fármaco antiepiléptico, daña la histología y cambia los patrones de fosforilación de la tirosina con el aumento del estrés oxidativo en los tejidos perirrenales. Este estudio tuvo como objetivo investigar el efecto del AVP en la microestructura, la fosforilación de la tirosina y la peroxidación lipídica del riñón de rata. Se dividieron ratas macho adultas en grupos control y tratados con AVP. Durante 10 días consecutivos fueron inyectadas por vía intraperitoneal con solución salina normal y 500 mg / kg de PC respectivamente (n = 7 cada uno). Se analizó el suero sanguíneo para determinar los niveles bioquímicos. Los tejidos renales se procesaron de forma rutinaria para la observación histológica. Las proteínas totales del riñón se extrajeron para analizar los niveles de malondialdehído (MDA) y la expresión de la fosforilación. Los resultados mostraron que el AVP disminuyó significativamente los niveles de glucosa en la sangre, mientras que tienden a aumentar el nitrógeno ureico y la creatinina. Los niveles de MDA en el grupo de AVP fueron significativamente más altos que los del control. La corteza renal de los animales tratados con AVP reveló vasodilataciones. Aunque la proporción de una expresión de proteína / actina de 72 kDa fosforilada renal no parece ser diferente en ambos grupos, el AVP disminuyó significativamente la intensidad de la actina beta. En conclusión, el AVP dilata la microvasculatura renal al aumentar el MDA, pero suprime la expresión de actina.

Research progress of terlipressin in the treatment of cirrhotic ascites-related complications / 中华肝脏病杂志

Ascites is the most common clinical symptom in the decompensated stage of patients with liver cirrhosis, and its co-existence in complex conditions, such as refractory ascites, hyponatremia, hepatorenal syndrome and other complications may harm seriously. Splanchnic vasodilation is the key pathological link of cirrhotic ascites-related complications and the treatment of this link can help to eliminate the symptoms of ascites and prevent the further deterioration of decompensated cirrhosis. This paper summaries the pharmacological basis, clinical evidence and application characteristics of a vasocative drugs-terlipressin in the treatment of cirrhotic ascites-related complications, and further analyzes the problems existing in the current research, then proposes a prospect.

Antithrombotic effect of epigallocatechin gallate on the patency of arterial microvascular anastomoses

BACKGROUND: Microvascular anastomosis patency is adversely affected by local and systemic factors. Impaired intimal recovery and endothelial mechanisms promoting thrombus formation at the anastomotic site are common etiological factors of reduced anastomosis patency. Epigallocatechin gallate (EGCG) is a catechin derivative belonging to the flavonoid subgroup and is present in green tea (Camellia sinensis). This study investigated the effects of EGCG on the structure of vessel tips used in microvascular anastomoses and evaluated its effects on thrombus formation at an anastomotic site. METHODS: Thirty-six adult male Wistar albino rats were used in the study. The right femoral artery was cut and reanastomosed. The rats were divided into two groups (18 per group) and were systemically administered either EGCG or saline. Each group were then subdivided into three groups, each with six rats. Axial histological sections were taken from segments 1 cm proximal and 1 cm distal to the microvascular anastomosis site on days 5, 10, and 14. RESULTS: Thrombus formation was significantly different between the EGCG and control groups on day 5 (P=0.015) but not on days 10 or 14. The mean luminal diameter was significantly greater in the EGCG group on days 5 (P=0.002), 10 (P=0.026), and 14 (P=0.002). Intimal thickening was significantly higher on days 5 (P=0.041) and 10 (P=0.02). CONCLUSIONS: EGCG showed vasodilatory effects and led to reduced early thrombus formation after microvascular repair. Similar studies on venous anastomoses and random or axial pedunculated skin flaps would also contribute valuable findings relevant to this topic.

Vasodilation and Reduction of Systolic Blood Pressure after One Session of High-Intensity Interval Training in Patients With Heart Failure with Preserved Ejection Fraction / Vasodilatação e Redução da Pressão Arterial Sistólica após uma Sessão de Treinamento Intervalado de Alta Intensidade em Pacientes com Insuficiência Cardíaca com Fração de Ejeção Preservada

Abstract Background: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial syndrome characterized by a limited exercising capacity. High-intensity interval training (HIIT) is an emerging strategy for exercise rehabilitation in different settings. In patients with HFpEF, HIIT subacute effects on endothelial function and blood pressure are still unknown. Objective: To evaluate the subacute effect of one HIIT session on endothelial function and blood pressure in patients with HFpEF. Methods: Sixteen patients with HFpEF underwent a 36-minute session of HIIT on a treadmill, alternating four minutes of high-intensity intervals with three minutes of active recovery. Brachial artery diameter, flow-mediated dilation, and blood pressure were assessed immediately before and 30 minutes after the HIIT session. In all analyses, p <0.05 was considered statistically significant. Results: There was an increase in brachial artery diameter (pre-exercise: 3.96 ± 0.57 mm; post-exercise: 4.33 ± 0.69 mm; p < 0.01) and a decrease in systolic blood pressure (pre-exercise: 138 ± 21 mmHg; post-exercise: 125 ± 20 mmHg; p < 0.01). Flow-mediated dilation (pre-exercise: 5.91 ± 5.20%; post-exercise: 3.55 ± 6.59%; p = 0.162) and diastolic blood pressure (pre-exercise: 81 ± 11 mmHg; post-exercise: 77 ± 8 mmHg; p = 1.000) did not change significantly. There were no adverse events throughout the experiment. Conclusions: One single HIIT session promoted an increase in brachial artery diameter and reduction in systolic blood pressure, but it did not change flow-mediated dilation and diastolic blood pressure.

Resumo Fundamento: Insuficiência cardíaca com fração de ejeção preservada (ICFEP) é uma síndrome multifatorial caracterizada por limitação ao exercício. O treinamento intervalado de alta intensidade (HIIT) é uma estratégia emergente para a reabilitação do exercício em diferentes contextos. Em pacientes com ICFEP, os efeitos subagudos do HIIT sobre a função endotelial e a pressão arterial ainda são desconhecidos. Objetivo: Avaliar o efeito subagudo de uma única sessão do HIIT sobre a função endotelial e a pressão arterial em pacientes com ICFEP. Métodos: Dezesseis pacientes com ICFEP foram submetidos a uma sessão de 36 minutos de HIIT em esteira rolante, alternando quatro minutos de intervalos de alta intensidade com três minutos de recuperação ativa. O diâmetro da artéria braquial, a dilatação mediada pelo fluxo e a pressão arterial foram avaliados imediatamente antes e 30 minutos após a sessão de HIIT. Em todas as análises, p <0,05 foi considerado estatisticamente significativo. Resultados: Houve aumento do diâmetro da artéria braquial (pré-exercício: 3,96 ± 0,57 mm; pós-exercício: 4,33 ± 0,69 mm; p < 0,01), e diminuição da pressão arterial sistólica (pré-exercício: 138 ± 21 mmHg; pós-exercício: 125 ± 20 mmHg; p < 0,01). A dilatação mediada por fluxo (pré-exercício: 5,91 ± 5,20%; pós-exercício: 3,55 ± 6,59%; p = 0,162) e pressão arterial diastólica (pré-exercício: 81 ± 11 mmHg; pós-exercício: 77 ± 8 mmHg; p = 1,000) não se alteraram significativamente. Não houve eventos adversos durante o experimento. Conclusões: Uma única sessão do HIIT promoveu aumento do diâmetro da artéria braquial e redução da pressão arterial sistólica, mas não alterou a dilatação mediada pelo fluxo e a pressão arterial diastólica.

Correlation of endothelial dysfunction measured by flow-mediated vasodilatation to severity of coronary artery disease

Objectives Brachial artery ultrasound imaging during reactive hyperemia is widely used tool for quantifying endothelium dependent vasomotion. Angiodefender device is used for non invasive determination of percentage flow mediated vasodilation (FMD). An attempt is made to study whether endothelial dysfunction determined by FMD of brachial artery predicts the presence or absence of coronary artery disease and its correlation with the severity of coronary artery disease. Methods One hundred six patients admitted between May 2014 and April 2015 who were posted for coronary angiography diagnosed to have chronic stable angina on clinical basis and/or by exercise stress test, for evaluation of coronary artery disease were submitted to standard clinical evaluation, calculation of percentage FMD by Angiodefender device. Statistical significance of difference of categorical variables was tested using Fisher’s exact test. Sensitivity, specificity, positive predictive value and negative predictive value of FMD were studied. Results There was no correlation between number of risk factors and percentage of FMD. Significantly higher proportion of cases with less FMD had higher prevalence of coronary artery disease and vice-versa. Significantly higher proportion of cases with positive stress test had less percentage of FMD and vice-versa. Significantly higher proportion of cases with less percentage of FMD and positive stress test had higher prevalence of obstructive coronary artery disease and vice-versa. Specificity was 100% when percentage of FMD was ≤10. Conclusions FMD an inexpensive and non-invasive test provides information regarding extent and severity of coronary artery disease.

The Arteriolar Vasodilatation Model of Vibrio cholerae Induced Diarrhoeal Disease

Secretory diarrhoeal disease caused by enterotoxins produced by pathogenic bacteria is characterised by severe fluid loss into the intestine. A prevalent explanation for such high rates of loss, such as occur in episodes of cholera, is that intestinal epithelial cells (enterocytes) actively secrete chloride ion into the lumen. Fluid is drawn into the lumen because of the osmotic pressure difference that is created across the mucosa. Widely proposed as the cause of many forms of secretory diarrhoea, the enterocyte based paradigm displaced an earlier model of secretion i.e. fluid filtration caused by increased capillary hydrostatic pressure, possibly coupled with increased hydraulic conductivity. This would be aggravated by any concurrent inhibition of fluid absorption if it occurred. In the earlier and alternative paradigm, pathophysiological reductions in smooth muscle tone elevate capillary pressure, thereby increasing the hydrostatic pressure gradient that forces fluid from the capillary into the interstitial space and thence into the lumen. In this review, the present and historical evidence for the vasodilatation view of secretory diarrhoeal disease is presented, together with past challenges of this concept, particularly those involving the erroneous equating of solute permeability with hydraulic conductivity. It can be seen that the physical forces model of altered Starling forces combined with enhanced fluid permeation explains more experimental findings than the cellular based enterocyte model can. Several key past papers advocating enterocyte secretion in which the capillary vasodilatation model was also discounted, were examined for the inherent fallacies within the arguments that were proposed. Where possible, quantitative arguments are proposed that indicate that is it the combination of capillary vasodilatation combined with increased tight junctional hydraulic conductivity that causes profuse secretion, made worse by any concurrent inability to absorb fluid. To assist the general physiological reader, an appendix reviews Bernoulli’s principle of flow within tubes and explains the arguably counter-intuitive phenomenon that vasodilatation increases capillary pressure because of a velocity reduction within a dilated segment.

Effects and mechanisms of mesenteric arterial rings vasodilation induced by protocatechuic aldehyde / 西安交通大学学报(医学版)

Objective To investigate the vasodilating effects of protocatechuic aldehyde (PCA ) on rat superior mesenteric arterial rings as well as its mechanism .Methods The tension of rat superior mesenteric arterial rings was recorded by a sensitive myograph system in vitro . We measured isometric tension changes in preconstricted rat superior mesenteric artery rings induced by potassium chloride (KCl ,60 mmol/L) ,serotomin (5-HT ,10-5 mol/L ) , and phenylephrine (PE , 10-5 mol/L ) after PCA treatment at different concentrations , respectively .We also observed vasodilating effects of PCA on KCl (60 mmol/L ) preconstricted rat superior mesenteric arterial rings after incubation with different inhibitors ,i .e .,L-NAME ,Indo ,ODQ ,4-AP (KV channel blocker) ,TEA (KCa channel blocker) ,BaCl2 (Kir channel blocker) ,and Glib (KATP channel blocker) ,respectively . Results PCA (10-6 -10-3 mol/L ) could relax KCl (60 mmol/L ) and 5-HT (10-5 mol/L ) preconstricted rat superior mesenteric arterial rings in a concentration-dependent manner . Indo of endothelial mechanism inhibitor blocked the vasodilating effect of PCA . 4-AP and BaCl2 of potassium ion channel inhibitors affected the vasodilatation induced by PCA in KCl (60 mmol/L)-preconstricted rat mesenteric artery .Conclusion PCA can relax KCl (60 mmol/L) ,or 5-HT preconstricted rat superior mesenteric arterial rings .This effect is associated with the inhibition of potassium channels and endothelial mechanism .

Chemical constituents and bioactive activities of Eleutherine americana / 中草药

Objective: To study the chemical constituents of Eleutherine americana. Methods: The compounds were isolated by various chromatographic techniques, including silica gel, TLC, sephadex LH-20, and semi-preparative HPLC, and their structures were identified by their physicochemical properties and 1H-NMR and 13C-NMR data. Results: Fifteen compounds were isolated from E. americana, which were germacrenin B (1), phaffiaol (2), 4,8-dihydroxy-3-methoxy-l-methylonthra-9,10-quinone-2-carboxylic acid methyl ester (3), 3-heptadecyl-5-methoxyphenol (4), ethyl linoleate (5), 3,5-dimethoxybiphenyl-4’-ol (6), karwinaphthol A (7), 5-hydroxylkarwinaphthol A (8), 3,4-dimethoxy-8-hydroxy-1-methyl-anthra-9,10-quinone-2-carboxylic acid methyl ester (9), isoeleutherin (10), eleutherin (11), isoeleutherol (12), naphtho-γ-lactone (+)-9-hydroxyeleutherol (13), senkyunone (14), and palmitoleic acid (15). Conclusion: Compounds 2, 4-7, and 13-15 were isolated from the genus for the first time. The compounds 3, 8, and 13 had strong vasodilator effects with diastolic rate of 85.3%, 81.8%, and 89.5%, respectively, which were basically equivalent to the positive drug of tanshinone IIA (86.3%).