Acetylcholine produces contractions mediated by the cyclooxygenase pathway in arterial vessels in the Chilean frog (Calyptocephalella gayi) / Acetilcolina produz contrações mediadas pela via da ciclooxigenase em vasos arteriais da rã chileno (Calyptocephalella gayi)

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.

Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study / Avaliação dos efeitos de sugamadex e dexmedetomidina intra-arterial: estudo experimental

Abstract Background: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Methods: Rabbits were randomly divided into 4 groups. Group Control (n = 7); no intervention performed. Group Catheter (n = 7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n = 7); rabbits were given 4 mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n = 7); rabbits were given 1 µg/kg dexmedetomidine into the central artery of the ear. After 72 h, the ears were amputated and histologically investigated. Results: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p < 0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Conclusion: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.

Resumo Justificativa: A injeção intra-arterial de medicamentos pode causar isquemia aguda e grave e resultar em morbidade e mortalidade. Não há informações na literatura que avaliem os efeitos endoteliais arteriais de sugamadex e dexmedetomidina. A hipótese de nosso estudo foi que dexmedetomidina e sugamadex causariam alterações histológicas na estrutura endotelial arterial quando administrados por via intra-arterial. Método: Os coelhos foram randomicamente divididos em quatro grupos: grupo controle (n = 7), sem intervenção; grupo cateter (n = 7), uma cânula foi inserida na artéria central da orelha e medicamentos não foram administrados; grupo sugamadex (n = 7), receberam 4 mg/kg de sugamadex na artéria central da orelha; grupo dexmedetomidina (n = 7), receberam 1 µg/kg de dexmedetomidina na artéria central da orelha. Após 72 horas, as orelhas foram amputadas e histologicamente examinadas. Resultados: Não houve diferença significativa entre os grupos controle e cateter referente aos escores histológicos. Os escores do dano causado ao endotélio e à membrana e fibra elásticas, da hipertrofia do músculo liso e do aumento do tecido conjuntivo foram significativamente maiores nos grupos dexmedetomidina e sugamadex do que nos grupos controle e cateter (p < 0,05). Não houve diferença significativa entre os grupos dexmedetomidina e sugamadex nos escores histológicos. Conclusão: A administração de sugamadex e dexmedetomidina a coelhos por via intra-arterial causou danos arteriais histológicos. Para entender as alterações histológicas causadas por sugamadex e dexmedetomidina com mais clareza, estudos experimentais adicionais são necessários.

Acetylcholine produces contraction mediated by cyclooxigenase pathway in arterial vessels in the marine fish (Isacia conceptionis) / Função vascular nas artérias do peixe marinos Isacia conceptionis

Preliminary studies showed that dorsal artery contraction mediated by acetylcholine (ACh) is blocked with indomethacin in intertidal fish (G. laevifrons). Our objective was to characterize the cholinergic pathway in several artery vessels of the I. conceptionis. Afferent and efferent branchial, dorsal and mesenteric arteries were dissected of 6 juvenile specimens, isometric tension studies were done using doses response curves (DRC) for Ach (10–13 to 10–3 M), and cholinergic pathways were obtained by blocking with atropine or indomethacin. CRC to ACh showed a pattern of high sensitivity only in efferente branchial artery and low sensibility in all vessels. Furthermore, these contractions were blocked in the presence of atropine and indomethacin in all vessels. Our results corroborate previous results observed in intertidal species that contraction induced by acetylcholine is mediated by receptors that activate a cyclooxygenase contraction pathway.

Estudos preliminares mostraram que a contração da artéria dorsal mediada por acetilcolina (ACh) é bloqueada com indometacina em peixes marinhos (G. laevifrons). Nosso objetivo foi caracterizar a via colinérgica em várias artérias de I. conceptionis. Artérias aferentes e eferentes branquiais, dorsais e mesentéricas foram dissecadas de 6 espécimes juvenis. Os estudos de tensão isométrica foram feitos utilizando-se a curva dose - resposta (CDR) para Ach (10–13 a 10–3M), e identificaram-se as vias colinérgicas, bloqueando com atropina e indometacina. CRC para ACh mostrou um padrão de alta sensibilidade na artéria eferentes branquiais e baixa sensibilidade em todos os vasos sanguineos. Essas contrações foram bloqueadas na presença de atropina e indometacina em todas as artérias avaliadas. Nossos resultados confirmam que a contração induzida por acetilcolina é mediada por receptores muscarínicos que ativam ciclo-oxigenase.

El consumo crónico de clorhidrato y/o pasta base de cocaína asocia envejecimiento arterial prematuro y aumento del riesgo cardiovascular / Chronic consumption of hydrochloride and / or cocaine base paste associates premature arterial aging and increased cardiovascular risk

Introducción: el consumo de cocaína en forma de clorhidrato (CC), y especialmente de su pasta base (PBC), es un problema sanitario mayor, entre otros factores, por su incidencia, repercusión y franja etaria a la que involucra. Múltiples efectos cardiovasculares han sido descritos en asociación con el consumo de CC, pero el impacto a corto/mediano plazo del uso crónico de CC y PBC en el sistema arterial en sujetos jóvenes no se ha estudiado. Objetivo: determinar la prevalencia de cambios (alteraciones) arteriales estructurales y/o funcionales en jóvenes consumidores de cocaína o sus derivados. Material y método: se incluyeron 29 sujetos (27 hombres; edad media/rango: 29/20-35 años) con criterios toxicológicos de dependencia a cocaína, más de dos años de consumo, y abstinencia menor a un mes. Se realizó evaluación clínica y paraclínica para cuantificar el riesgo cardiovascular global (escore de riesgo de Framingham [EF] para enfermedad cardiovascular a diez años). Los estudios incluyeron determinación de: 1) presencia de placas de ateroma carotídeas y espesor íntima-media carotídeo (EIMC; ecografía modo-B color y software específico). 2) Rigidez aórtica regional (mediante velocidad de la onda del pulso, [VOP]). 3) Presión de pulso aórtica central (tonometría de aplanamiento). 4) Índice tobillo-brazo (oscilometría). 5) Reactividad vascular, función endotelial, por vasodilatación mediada por flujo (DMF; ecografía modo-B y software específico). Se determinó la edad vascular (EV) mediante análisis multiparamétrico. El envejecimiento arterial precoz (EAP) se definió como la diferencia entre la EV y la edad cronológica. Los datos obtenidos se compararon con valores de normalidad (sujetos control). Resultados: de los 29 pacientes, 10 fueron consumidores de CC, 3 de PBC y 16 de ambas sustancias. El 90% eran fumadores de cigarrillos (promedio de consumo: 14,4 cigarrillos/día). Si bien ningún paciente presentó VOP >10 m/s (punto de normalidad aceptado por la Sociedad Europea de Cardiología), 63,6% tuvo niveles de VOP entre el percentil (p)50 y el p90 de la población control de referencia, y 13,6% por encima del p90 de la misma población, indicando que el 77,2% de los mismos presentaron VOP >p50. Respecto del EIMC, un 8% de los pacientes estudiados tuvo niveles > 0,9 mm, y 69% niveles por encima del p95 de la población de referencia, para sexo y edad.. El análisis de la función endotelial mostró que 13,6% de los pacientes no presentó dilatación arterial (DMF £ 0%) y 36% presentó DMF £ 5%. Finalmente, el 33% de los pacientes presentó niveles de presión de pulso aórtica por encima del nivel umbral (p95), para sexo y edad. La EA fue de 37,1 ± 8,4 años, indicando la existencia de un EAP de 8,1 ± 6,2 años (rango: 3-24 años). Conclusión: los usuarios de cocaína mostraron cambios subclínicos perjudiciales a nivel arterial que se asocian a mayor riesgo cardiovascular. Sus parámetros arteriales presentaron niveles compatibles con los existentes en una población control con una edad de 8,1 ± 6,2 años mayor que la estudiada, indicando que los consumidores de CC y PBC podrían presentar "envejecimiento arterial precoz".

Introduction: cocaine consumption, in particular cocaine base paste, is a major health problem, among other factors, its incidence, impact, and the age group involved. Multiple cardiovascular effects have been described in association with cocaine use but the impact in the short/medium-term chronic use of hydrochloride cocaine and cocaine base paste in the arterial system in young subjects has not been studied.Objective: to determine the prevalence of changes (alterations) arterial structural and/or functional in young cocaine or its derivatives users Method: 29 subjects (age: 20-35 years; 27 men) with toxicological criteria for cocaine dependence, over 2 years old and less than one month withdrawal were included. Clinical and paraclinical evaluation was conducted to quantify the global cardio-vascular risk (10-years Framingham Risk Score for cardiovascular disease). The studies included determination of: 1) presence of carotid atheromatous plaques and carotid intima-media thickness (CIMT; color and B-mode ultra sound and specific software), 2) assessment of regional aortic stiffness by pulse wave velocity (PWV), 3) evaluation of central aortic pulse pressure by applanation tonometry, 4) ankle-brachial index, by oscillometry and 5) vascular reactivity (endothelial function) by flow mediated dilatation (FMD) with B-mode ultra sound and specific software. The vascular age (VA) was calculated by multiparametric analysis. The arterial aging (AA) was defined as the difference between the VA and chronological age. The obtained data were compared with normal values (control subjects). Results: 29 patients were evaluated, 10 patients were users of hydrochloride cocaine, 3 cocaine base paste and 16 of both substances. 90% of patients were smokers (mean consumption: 14.4 cigarettes/day). Although no patient had PWV values above 10 m/s, 63,6% had levels of PWV between p50 and p90 and 13,6% above the p90, indicating that 77% of them presented by PWV over p50. Regarding the CIMT, 8% of the patients studied had levels above 0,9 mm, and 69% higher than p75 levels to age and sex. The endothelial function analysis showed that 13,6% of patients had no arterial dilation (FMD £ 0%) and 36% presented a £ 5% FMD. Finally, 33% of patients had levels of aortic pulse pressure above the threshold level (p95 of the reference control group) for gender and age. The AA was 37.1±8.4 years, indicating the existence of early arterial aging 8.1±6.2 years (range 3-24 years). Conclusion: cocaine users showed adverse subclinical level changes of the structure and function of the arteries which is associated with increased cardiovascular risk. The levels obtained for different arterial parameters evaluated were consistent with those in a control population with an age 8.1±6.2 years older than the study, indicating that users of hydrochloride cocaine and cocaine base paste might present "early arterial aging."

Vascular function in arteries of intertidal fish Girella laevifrons (Kyphosidae) / Função vascular nas artérias do peixe marinho Girella laevifrons (Kyphosidae)

Preliminary studies showed that dorsal artery contraction mediated by acetylcholine (ACh) is blocked with indomethacin in intertidal fish (Girella laevifrons). Our objective was to characterise the cholinergic pathway in several artery vessels of the G. laevifrons. Afferent and efferent branchial, dorsal and mesenteric arteries were dissected of 6 juvenile specimens, isometric tension studies were done using dose response curves (DRC) for Ach (10–13 to 10–3 M), and cholinergic pathways were obtained by blocking with atropine or indomethacin. CRC to ACh showed a pattern of high and low sensitivity. Furthermore, these contractions were blocked in the presence of atropine and indomethacin in all vessels. Our results suggest that contraction observed with acetylcholine is mediated by receptors that activate a cyclooxygenase contraction pathway.

Estudos preliminares mostraram que a contração da artéria dorsal mediada por acetilcolina (ACh) é bloqueada com indometacina em peixes marinhos Girella laevifrons. Nosso objetivo foi caracterizar a via colinérgica em várias artérias de G. laevifrons. Artérias aferentes e eferentes branquiais, dorsais e mesentéricas foram dissecadas de 6 espécimes juvenis. Os estudos de tensão isométrica foram feitos utilizando-se a curva dose - resposta (CDR) para Ach (10–13 a 10–3M), e identificaram-se as vias colinérgicas, bloqueando com atropina e indometacina. CRC para ACh mostrou um padrão de alta e baixa sensibilidade. Essas contrações foram bloqueadas na presença de atropina e indometacina em todas as artérias avaliadas. Nossos resultados sugerem que a contração observada com acetilcolina é mediada por receptores muscarínicos que ativam uma ciclo-oxigenase.

Drag reduction by polyethylene glycol in the tail arterial bed of normotensive and hypertensive rats

This study was designed to evaluate the effect of drag reducer polymers (DRP) on arteries from normotensive (Wistar) and spontaneously hypertensive rats (SHR). Polyethylene glycol (PEG 4000 at 5000 ppm) was perfused in the tail arterial bed with (E+) and without endothelium (E-) from male, adult Wistar (N = 14) and SHR (N = 13) animals under basal conditions (constant flow at 2.5 mL/min). In these preparations, flow-pressure curves (1.5 to 10 mL/min) were constructed before and 1 h after PEG 4000 perfusion. Afterwards, the tail arterial bed was fixed and the internal diameters of the arteries were then measured by microscopy and drag reduction was assessed based on the values of wall shear stress (WSS) by computational simulation. In Wistar and SHR groups, perfusion of PEG 4000 significantly reduced pulsatile pressure (Wistar/E+: 17.5 ± 2.8; SHR/E+: 16.3 ± 2.7 percent), WSS (Wistar/E+: 36; SHR/E+: 40 percent) and the flow-pressure response. The E- reduced the effects of PEG 4000 on arteries from both groups, suggesting that endothelial damage decreased the effect of PEG 4000 as a DRP. Moreover, the effects of PEG 4000 were more pronounced in the tail arterial bed from SHR compared to Wistar rats. In conclusion, these data demonstrated for the first time that PEG 4000 was more effective in reducing the pressure-flow response as well as WSS in the tail arterial bed of hypertensive than of normotensive rats and these effects were amplified by, but not dependent on, endothelial integrity. Thus, these results show an additional mechanism of action of this polymer besides its mechanical effect through the release and/or bioavailability of endothelial factors.

Effects of Lowering Dialysate Calcium Concentrations on Arterial Stiffness in Patients Undergoing Hemodialysis

BACKGROUND/AIMS: We assessed changes in hemodynamic and arterial stiffness parameters following reductions of dialysate calcium concentrations in patients undergoing hemodialysis. METHODS: In this prospective study, 20 patients on maintenance hemodialysis (10 females, 10 males) with dialysate calcium concentrations of 1.75 mmol/L were enrolled. At the start of the study, the dialysate calcium level was lowered to 1.50 mmol/L. Serial changes in biochemical, hemodynamic, and arterial stiffness parameters, including pulse wave velocity (PWV) and augmentation index (AIx), were assessed every 2 months for 6 months. We also examined changes in the calcification-inhibitory protein, serum fetuin-A. RESULTS: During the 6-month study period, serum total calcium and ionized calcium decreased consistently (9.5 +/- 1.0 to 9.0 +/- 0.7, p = 0.002 vs. 1.3 +/- 0.1 to 1.1 +/- 0.1, p = 0.035). Although no apparent changes in blood pressure were observed, heart-femoral PWW (hf-PWV) and AIx showed significant improvement (p = 0.012, 0.043, respectively). Repeated-measures ANOVA indicated a significant effect of lowering dialysate calcium on hf-PWV (F = 4.58, p = 0.004) and AIx (F = 2.55, p = 0.049). Accompanying the change in serum calcium, serum fetuin-A levels significantly increased (95.8 +/- 45.8 pmol/mL at baseline to 124.9 +/- 82.2 pmol/mL at 6 months, p = 0.043). CONCLUSIONS: Lowering dialysate calcium concentration significantly improved arterial stiffness parameters, which may have been associated with upregulation of serum fetuin-A.

Epinephrine's effect in varying concentrations on the end artery organ in an animal model

To determine the concentration of epinephrine that causes end artery necrosis and ischemia. An experimental study. Animal Laboratory of Khordad Hospital, Tehran, Iran, from September 2007 to June 2008. This study was done on 54 ear flaps from 9 rabbits [9 [rabbits] x2 [ears] x3 [splits] =54] divided into three groups of 18 ear flaps each. Nine of the ear flaps were randomized as control and nine of them were randomized as study group. The different concentrations of epinephrine and lidocaine 1% were injected in study groups but only 1% lidocaine was injected in control groups. Study group 1 received 1/200000, group 2 received 1/100000 and group 3 received 1/500000 concentration of epinephrine respectively. There was no evidence of necrosis in the control and study groups 1 and 2. However, 4 out of 9 of the ear flaps showed clear evidence of tissue necrosis in group 3. Injecting epinephrine in 1/200000 and 1/100000 concentrations had no side effect for the end artery of the rabbit ear flaps, but 1/50000 concentration is shown that it can cause tissue necrosis. Further studies need to be done in order to find out the effects of epinephrine with the same concentrations on the human end artery

Differences in functional and structural properties of segments of the rat tail artery

The investigation of resistance vessels is generally costly and difficult to execute. The present study investigated the diameters and the vascular reactivity of different segments of the rat tail artery (base, middle, and tail end) of 30 male Wister rats (EPM strain) to characterize a conductance or resistance vessel, using a low-cost simple technique. The diameters (mean ± SEM) of the base and middle segments were 471 ± 4.97 and 540 ± 8.39 µm, respectively, the tail end was 253 ± 2.58 µm. To test reactivity, the whole tail arteries or segments were perfused under constant flow and the reactivity to phenylephrine (PHE; 0.01-300 µg) was evaluated before and after removal of the endothelium or drug administration. The maximal response (Emax) and sensitivity (pED50) to PHE of the whole tail and the base segment increased after endothelium removal or treatment with 100 µM L-NAME, which suggests modulation by nitric oxide. Indomethacin (10 µM) and tetraethylammonium (5 mM) did not change the Emax or pED50 of these segments. PHE and L-NAME increased the pED50 of the middle and the tail end only and indomethacin did not change pED50 or Emax. Tetraethylammonium increased the sensitivity only at the tail end, which suggests a blockade of vasodilator release. Results indicate that the proximal segment of the tail artery possesses a diameter compatible with a conductance vessel, while the tail end has the diameter of a resistance vessel. In addition, the vascular reactivity to PHE in the proximal segment is nitric oxide-dependent, while the tail end is dependent on endothelium-derived hyperpolarizing factor.

Study on the effect of oral hypoglycaemic agents on arterial stiffness among Malays with type II diabetes mellitus

To determine the effect of two regimens of oral hypoglycaemic agents: sulphonylurea monotherapy and metformin in combination with sulphonylurea on arterial stiffness. A case control study was conducted at the Family Medicine and Diabetic Clinic, HUSM from May 2004 until May 2005. Sixty subjects receiving sulphonylurea alone and ninety subjects on combination therapy with metformin participated in this study. A simple random sampling method using a draw lot was used to select 51 subjects for each group. Augmentation index [AI] was measured using the Sphygmocor apparatus and all measurements were performed by the investigators after an earlier validation study. The mean augmentation index measurements were analyzed. The mean AI values of diabetic subjects treated with sulphonylurea monotherapy and a combination with metformin were 140.51 +/- 11.42 vs 140.14 +/- 12.86, p= 0.877. AI values were significantly higher in females compared with males [143.23 +/- 10.60 vs 135.82 +/- 13.01, 95% CI: -12.07, -2.73, p = 0.002]. Duration of diabetes [in years] was significantly less [3.46 +/- 3.16 vs 5.41 +/- 3.66, p = 0.005] for sulphonylurea monotherapy patients compared with combination therapy patients. This study shows that sulphonylurea monotherapy and metformin in combination with sulphonylurea have similar effects on arterial stiffness in type 2 diabetes subjects. Diabetes is associated with a greater arterial stiffness in women compared with men

The Effects of Low Calcium Dialysate on Arterial Compliance and Vasoactive Substances in Patients with Hemodialysis

BACKGROUND: Considering that dialysate calcium concentration is potentially a main determinant of the serum ionized calcium level and vasoconstriction is associated with the blood calcium concentration, we conducted a study to evaluate the interdialytic effects of treatment with a low calcium dialysate (LdCa, 1.25 mmol/L) on the changes in arterial compliance (AC), blood pressure (BP), biochemical parameters and vasoactive substances. METHODS: Eight hemodialysis (HD) patients (mean age: 46.8 +/- 13.7 years, 4 men and 4 women) were included in the study. AC, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), serum ionized Ca, intact-PTH, serum nitric oxide and aldosterone were compared after 10 sessions of treatment with LdCa. Right carotid artery diameter was measured 3 times using a real time B-mode ultrasound imager (Hewlett-Packard Sonos 2000 (R) ) and AC was calculated using the Hayoz method. RESULTS: 1) AC was recorded as 0.140 (0.080-0.170) mm2/kPa at the baseline (1.75 mmol/L calcium dialysate), 0.170 (0.050-0.290) mm2/kPa after LdCa treatment (p< 0.05 versus baseline), and 0.140 (0.070-0.250) mm2/kPa following the HdCa treatment (p< 0.05 versus LdCa data). 2) MAP and PP were calculated at 114.12 +/- 10.56 mmHg and 63.50 +/- 10.87 mmHg at the baseline; 98.37 +/- 15.14 mmHg and 56.50 +/- 5.95 mmHg after LdCa treatment (p< 0.05 versus baseline) ; and 115.75 +/- 9.64 mmHg and 62.00 +/- 15.71 mmHg following HdCa treatment (p< 0.05 versus LdCa data). 3) Serum ionized Ca and intact-PTH were measured at 4.66 +/- 0.40 mg/dL and 25.08 +/- 16.44 pg/mL at the baseline; 4.45 +/- 0.28 mg/dL and 90.71 +/- 27.03 pg/mL after LdCa treatment (p< 0.05 versus baseline) ; and 4.65 +/- 0.43 mg/dL and 24.08 +/- 15.44 pg/mL following HdCa treatment (p< 0.05 versus LdCa data). 4) Serum aldosterone concentration was 300.8 (65.5-836.1) pg/mL at the baseline, and 220.2 (42.8-527.9) pg/mL after LdCa treatment (p< 0.05). CONCLUSION: There were favorable changes in AC, BP, biochemical parameters after treatment with LdCa. These changes may be associated with the reduction in serum ionized calcium and decreased serum aldosterone concentration.

Testosterone Causes Simultaneous Decrease of Ca2+i and Tension in Rabbit Coronary Arteries: by Opening Voltage Dependent Potassium Channels

The relationship between the level of testosterone and the incidence of coronary heart disease is still controversial in the view of the results of clinical and epidemiologic studies. This uncertainty might be partly due to relatively small number of experimental studies undertaken to investigate the cellular mechanism underlying the vascular responses to testosterone. To further investigate the cellular mechanisms of testosterone with respect to vascular response, we investigated the effect of testosterone on contractility and intracellular Ca2+ regulation in a rabbit coronary artery and evaluated the underlying mechanism of testosterone-induced changes of coronary vascular tone by using various pharmacological blockers. Testosterone was found to relax rabbit coronary arteries in a dose-dependent manner, and no significant difference was found in the relaxation response to testosterone with or without endothelium. Similar results were obtained in male and non-pregnant female rabbit coronary arteries. The relaxation response of rabbit coronary arteries to testosterone was greater for PGF2alpha-contracted rings than for KCl contracted rings, which suggest the involvement of K+ channels. Furthermore, the relaxation response to testosterone was significantly reduced by 4-aminopyridine, a sensitive blocker of voltage dependent K+ channels, but not by low doses of tetraethylammonium or iberiotoxin, a Ca2+ activated K+ channel blocker. Testosterone simultaneously reduced the intracellular Ca2+ concentration ([Ca2+]i) and tension, and 4-AP effectively antagonized the testosterone-induced change of [Ca2+]i and tension. Therefore, it may be concluded that the stimulation of voltage dependent K channels is responsible, at least in part, for the testosterone-induced relaxation of rabbit coronary arteries.

Assessment of perindopril's efficacy on arterial distensibility in mild to moderate hypertension.

OBJECTIVE: Angiotensin Converting Enzyme Inhibitors (ACEIs) have been clearly proven to be effective in blood pressure control and haemodynamic control in heart failure patients. Moreover, there is evidence that ACEIs, both in animal models and in humans, also possess the ability to reduce remodeling in cardiovascular structures. Therefore, the reduction of the occurrence of arterial stiffness, leading to an increase in distensibility, is also anticipated. METHOD: Other than physically measuring arterial wall, the assessment of Pulse Wave Velocity (PWV) is also a widely used index of arterial distensibility, which deteriorates through the course of remodeling. To determine the efficacy of a particular ACEI, perindopril, in increasing arterial distensibility, thus reducing PWV, a 6-month multi-center study was conducted in 146 patients with mild to moderate hypertension. The study population consisted of 70 men and 76 women, aged 56.36 (SD 9.4, range 28-73) years. 73 patients were newly diagnosed, 65 were treated patients but the blood pressure was not controlled, and 8 were treated patients with their blood pressure controlled but with adverse effects in need of switching treatment regimens. RESULTS: Mean blood pressure at the beginning of the study was 164.25/97.49 mmHg and 11.71 m/s (SD 2.29 range 7.35-20.12 m/s) in mean PWV. Perindopril was prescribed tritrating from 4 mg/day to 8 mg/day and adding a diuretic. 106 patients completed the study with 76.4 per cent of patients having their blood pressure controlled (Mean Blood pressure 138.6/85.18 mmHg, SD 11.34 and 7.10 Range 110-170/70-110 mmHg) (p<0.05). Mean PWV reduced to 10.56 m/s (-9.89%) (SD 1.84 range 7.27-15.96 m/s) (p<0.05). CONCLUSION: Anti-hypertensive treatment with perindopril for 6 months was effective in controlling blood pressure and reducing Pulse Wave Velocity reflecting the increase of arterial distensibility.

Sulfhydryl modification affects coronary artery tension by changing activity of delayed rectifier K+ current

It has been reported that a change in the cellular redox state may be involved in the regulation of vascular tone, but the underlying mechanism is not fully understood. The present study was designed to investigate the cellular effect of sulfhydryl modifying agents in the coronary artery of rabbit using the tension measurement and whole cell clamping method. The application of diamide, a sulfhydryl oxidizing agent, relaxed the endothelium denuded coronary arteries in a dose dependent manner. The fact that this diamide-induced relaxation was significantly attenuated by a pretreatment of 4-AP, and the coronary arteries precontracted with 100 mM K+ instead of histamine, suggests the involvement of 4-AP sensitive K+ channels in the diamide-induced relaxation of coronary arteries. Whole cell patch clamp studies revealed that the 4-AP sensitive IdK was significantly enhanced by the membrane permeant oxidizing agents, diamide and DTDP, and were reversed by subsequent exposure to the reducing agent, DTT. Neither the membrane impermeant oxidizing or reducing agents, GSSG or GSH, had any effect on the activity of IdK, indicating that intracellular sulfhydryl modification is critical for modulating IdK activity. The Diamide failed to significantly alter the voltage dependence of the activation and inactivation parameters, and did not change the inactivation process, suggesting that diamide increases the number of functional channels without altering their gating properties. Since IdK has been believed to play an important role in regulating membrane potential and arterial tone, our results about the effect of sulfhydryl modifying agents on coronary arterial tone and IdK activity should help understand the pathophysiology of the diseases, where oxidative damage has been implicated.

Influence of moderate cooling (37§C-25§C) on the reactivity of isolated rat tail artery

The aim of the investigation was to examine the effects of cooling on the tail artery regarding the scarceness of such studies in spite of the essential thermoregulatory role played by this vessel. Segments of the proximal portion were suspended isometrically in medium containig 1.25 mM Ca. Lowering the temperature to 25 degrees Celsius increased the sensitivity and maximum strength of the adrenaline concentration-effect curves. These changes were reversed by warming to 37 degrees Celsius. Cocaine attenuated the increase of sensitivity without changing the increase of the maximum response. Either the sensitivity and strength of the responses to phenylephrine and serotomin were increased by cooling. Clonidine evoked weak contractions in 18 out of 38 experiments. After cooling, the responses persisted only in 7 arteries and the strength was almost halved. Responses to field eletric stimulation at 25 degrees Celsius exhibited a pronounced increase of strength and a small increase of sensitivity. -log Kb for prazosin against adrenaline was encreased by cooling (8.7 and 9.1 at 37 degrees Celsius and 25 degrees Celsius C, P<0.01). After partial receptor inactivation using phenoxybenzamine, the dissociation-constant (KA) indicated a moderate affinity for phenylephrine that was not changed by cooling (4.1 and 4.2 x 10(-6) at 37 degrees Celsius respectively). Receptor reserve and occupancy at EC(50) also remained unchanged at 25 degrees Celsius. It can be concluded that: 1) cooling increases the tail artery reactivity, partly as a consequence of the inhibition of adrenergic neuronal uptake; 2) responsiveness to alpha 2-agonists is not in volved in the effects of cooling whereas the role of alpha 1-adrenoceptor could not be properly clarified; 3) cooling may facilitate some steps of the contractile activation beyond the agonist-receptor interaction.

Nonspecific blockade of vascular free radical signals by methylated arginine analogues

Methylated arginine analogues are often used as probes of the effect of nitric oxide; however, their specificity is unclear and seems to be frequently overestimated. This study analyzed the effects of N G -methyl-L-arginine (L-NMMA) on the endothelium-dependent release of vascular superoxide radicals triggered by increased flow. Plasma ascorbyl radical signals measured by direct electron paramagnetic resonance spectroscopy in 25 rabbits increased by 3.8 ñ 0.7 nmol/l vs baseline (28.7 ñ 1.4 nmol/l, P<0.001) in response to papaverine-induced flow increases of 121 ñ 12 por cento. In contrast, after similar papaverine-induced flow increases simultaneously with L-NMMA infusions, ascorbyl levels were not significantly changed compared to baseline. Similar results were obtained in isolated rabbit aortas perfused ex vivo with the spin trap Ó-phenyl-N- tert -butylnitrone (N = 22). However, in both preparations, this complete blockade was not reversed by co-infusion of excess L-arginine and was also obtained by N-methyl-D-arginine, thus indicating that it is not related to nitric oxide synthase. L-arginine alone was ineffective, as previously demonstrated for N G -methyl-L-arginine ester (L-NAME). In vitro , neither L-arginine nor its analogues scavenged superoxide radicals. This nonspecific activity of methylated arginine analogues underscores the need for careful controls in order to assess nitric oxide effects, particularly those related to interactions with active oxygen species

Reactivity of the isolated perfused rat tail vascular bed

Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg) and heparinized (500 U). The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 muM EDTA at 36 degrees Celsius and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE) (0.5, 1,2 and 5 mug, bolus injection) was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min). The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5,2,2.5,3 and 3.5 ml/min) at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM) in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 mug/ml). There was an enhancement of the effects of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity.

Primary segmental infarction of the greater omentum

Along with the presentation of another patient, we have reviewed a total of 146 cases of primary [idiopathic] segmental infarction of the greater omentum. The clinical findings, possible etiology and new ways to diagnose this clinical entity are described. Spontaneous infarction of the greater omentum may occur more often than is suspected. Surgeons rarely mention the appearance of the omentum in their operative notes. It seems reasonable, therefore, to propose that whenever a patient is operated upon for acute appendicitis and a normal appendix is found, a thorough inspection be made of the omentum

Effect of acute footshock stress on the responsiveness of the isolated rat tail artery to phenylephrine and epinephrine

The effects of acute footshock stress on the sensitivity of the isolated rat tail artery were studied. Footshock stress applied to male Wistar rats (200-300 g) causes subsensitivity to the vasoconstrictor effects of phenylephrine and epinephrine. No significant changes in the pA2 cvalues of prozosin were detected, using epinephrine as the agonist. Footshock stress-induced subsensitivity ot epinephrine was not affected by the calcium entry blocker nifedipine. However, nifedipine significantly depressed the maximum response to epinephrine in tail arteries isolated from acute footshock-stressed rats. The present results suggest that acute footshock stress-induced reduced sensitivity to phenylephrine and epinephrine may not be only related to events at the alpha-adrenoreceptor level. The nifedipine-induced depression of the maximum response to epinephrine suggests a role for the calcium mobilization processess in the vascular responsiveness during acute stress