Cardiovascular diseases are the main cause of mortality in most countries Comparing with age matched men the incidence of these diseases in fettling women and menopause women who take estrogen is low. This suggests a protective effect for estrogen in cardiovascular system. However the exact mechanism of this protective effect is not elucidated and is controversial. One of the possible mechanisms is the direct relaxing effect of es1rogen on vascular smooth muscle. The present study aims to identity the possible mechanism(s) of the vasorelaxant effect of 17B-estradiol on rat aorta. Rings of aorta 3-5 mm wide were prepared from male Wistar rats (250-350 g) and equilibrated in Krebs' solution under 2g tension (37°C; 95% O2, 5% CO2) for 60 min. Rings were contracted with. PGF2 (10 µM), an approximately EC80 concentration. When contraction was stable 17 B-estradiol was applied for 40 minutes. Relaxation was expressed as % reversal of contraction. For studying the possible effect of endothelium, prostaglandins, nitric oxide and classic estrogen receptors in the vasorelaxant effect of 17B-estradiol, the relaxant effect was assayed again in the absence of endothelium, and in the presence of indomethacin. N-nitro-L-arginine methyl ester (L-NAME). methylene blue, puromycin, actinomycin-D, cyclohexamide and tamoxifen. Denuding the endothelium of aortic rings or incubating them with indomethacin, L-NAME, methylene blue, puromycin, actinomycin-D, cyclohexamide and tamoxifen did not alter the vasorelaxant effect of 17B-estradiol significantly (P>0.05). Therefore, it would suggest that this acute relaxing effect of estrogeil is independent of endothelium, prostaglandin production, NO synthesis and genomic pathways. Further studies are needed to clarify the mechanism(s) by which 17B-estradiol relaxes vascular smooth muscle.

Drug design is generally achieved through trial and error methods, which is a time and resource consuming process and novel methods are needed to improve it. Mathematical modelling is one of the possible solutions to speed up this process. In this study, we have presented Box-Jenkins model, to predict the vasorelaxant activity (pEC50) of a set of benzopyrane compounds. We used the HyperChem software to extract the molecular features of these compounds (51 molecules); then these features were used to generate the Box-Jenkins model. The dataset was divided into three groups: 37 for training, 9 for prediction and 5 for validation. The absolute relative deviation of the predicted values was 4.8% and 4.1% for validation and predicton sets, respectively. The correlation coefficient between the predicted points and the experimental values was 0.9657, revealing that the proposed model is capable of representing pEC50 of benzopyranes and could be used to speed up drug discovery processes.

Objective: In a previous work, we showed that asafoetida essential oil (AEO), from oleo-gum resin of Ferula asafoetida L. from the Apiaceae family, has a vasodilatory effect. This effect was both endothelium-dependent and endothelium-independent. The present study was designed to determine whether potassium channels and intracellular calcium release contribute to AEO-induced vasodilation. Materials and Methods: Rats' thoracic aorta were isolated and denuded. Following induction of contraction by potassium chloride (60 mM), concentration-response curve was plotted by the cumulative addition of AEO (0. 625-80 μ l/l to the medium of rings. The vasodilatory effect of AEO was assessed before and after addition of phenylephrine and potassium channel blockers (including barium chloride (BC), 4-aminopyridine (4A) and glibenclamide (Gl)). Results: AEO relaxed the precontracted rings in a concentration-dependent manner (IC50=23 μ l/l). All potassium channel blockers significantly attenuated the vasodilatory activity of AEO when they were added to rings medium before addition of KCl (p<0. 01, 4A and Gl groups and p< 0. 001, BC group vs. control group) but not after that. In contrast to K channel blockers, adding AEO before or after phenylephrine, the tension was reduced significantly (p<0. 05 vs. the control group). Conclusion: The findings of this study indicated that the vasodilatory effect of AEO on denuded-endothelium aortic ring was mediated through activation of potassium channels and reduced intracellular calcium release.

Background & Objectives: There are some reports on hypotensive and antispasmodic effects of Teucrium polium. The aim of this study was to investigate the vasorelaxant effect of Teucrium polium extract on rat thoracic aorta.Materials & Methods: Sixty four male Wistar rats were divided randomly into 8 groups. The relaxant effects of cumulative concentrations of the extract (1, 2, 4 and 8 mg/ml) on phenylephrine (PE) and potassium chloride (KCl) induced contraction were evaluated in endothelium-intact and -denuded aortas. In another set of experiments the effect of extract (8 mg/ml) on PE and KCl induced contraction in the presence of cumulative calcium concentrations (from 10-5 to 10-2 M) were investigated. Then the effect of the extract on aorta precontracted by PE in the presence of L-NAME (L-NG-Nitroarginine methyl ester, hydrochloride) (100mM) and indomethacin (10mM) were studied.Results: The cumulative concentrations of extract induced a concentration dependent relaxation in the aorta precontracted by PE and KCl. The extract reduced PE and KCl induced contraction in presence of cumulative calcium concentrations. All the extract concentrations (except 1 mg/ml) significantly relaxed PE induced contraction in the presence of L-NAME. The extract significantly relaxed the precontracted aorta by phenylephrine in the presence of indomethacin except by 1 and 2 mg/ml concentrations.Conclusion: The results showed that the extract had vasorelaxant effect on aorta precontracted by PE and KCl. The relaxation mainly was mediated by inhibition calcium influx in vascular smooth muscle cells. It seems the vasorelaxant effect of extract at lower concentrations mediated by nitric oxide and prostacyclin.

Objectives: Cardiovascular disease is a major cause of morbidity and mortality in the world. Compared to men of similar age, pre-menopausal women have significantly lower incidence of adverse cardiovascular event including coronary heart disease, essential hypertension and stroke. The incidence of these disorders increases in women with absence of functional ovaries. Estrogen therapy of post menopausal women reduces the incidence of these diseases. This beneficial effect of estrogen may have several mechanisms. The vas ore lax ant effect of estrogens on vasculature is one f the important cardio protective effects. The exact underlying molecular mechanism of this estrogen-induced vasodilatation has not yet been determined. Considering the important roles of veins in preload and heart failure and coronary artery diseases, in this study the acute relaxant effect of 17 b-estradiol and role of endothelium and cyclic guanosin mono phosphate (cGMP) on this effect has been investigated on human saphenous vein. Methods: Rings of human saphenous vein with 3-5 mm length were prepared and equilibrated in Krebs solution under 3 g tension (37°C; 95% O2 ; 5% CO2) for 60 min. In the various experiments, the vascular rings were contracted with prostaglandin F2a(PGF2a, 1.5µM) or potassium chloride (KCl, 60 mM). When contraction was stable 17 b-estradiol was applied for 40 minutes in the presence or absence of endothelium and different inhibitors. Relaxation was expressed as % reversal of contraction induced by vasoactive agents. Results: 17 b-estradiol (5-40 µM) elicited a concentration-dependent relaxation of KCI- and PGF2a -induced active tone in human saphenous vein rings. Incubation of veins for 20 min with methylen blue or N-nitro-L-arginine methyl ester (L-NAME) reduced the relaxant effect of estrogen, significantly (p<0.05). This reduction was disappeared by denuding endothelium. However, when intact tissues were incubated with 10 µM indomethacin, cycloxygenase inhibitor or 1µM KT5823, a protein kinase G inhibitor or cyclohexamide (100 µM) or puromycin (10µM) protein synthetase inhibitors, the vasorelaxant effect of 17 b-estradiol on PGF2a -induced contraction was not modified significantly (p>0.05). Conclusion: These results suggest that 17 b-estradiol induces dose dependent vasorelaxant effect in human saphenous vein, at least partially, by nitric oxide production and this relaxant effect is independent of cGMP, cycloxygenase or genomic pathways.

Introduction: Considering the higher incidence of atherosclerosis and cardiovascular disorders in diabetes mellitus and the role of vasorelaxation disturbance in the development of these complications, this study was conducted to evaluate the effect of two-month oral administration of Marrubium vulgare (MV) on the vasorelaxation response of isolated aorta in experimental model of diabetes mellitus in rats.Methods: In this experimental study, 32 male Wistar rats were randomly divided into four groups: control, MV-treated control, diabetic, and MV-treated diabetic groups. For induction of diabetes, streptozotcin (STZ) was intraperitoneally administered (60mg/kg). MV-treated groups received MV mixed with standard pelleted food at a weight ratio of 1/15. After 2 months, relaxation response of KCI-and noradrenaline-precontracted aortic rings was determined after addition of acetylcholine using isolated tissue setup.Results: Comparing to one week before test serum glucose level showed a significant increase in diabetic group at 4th and 8th weeks (P<0.001), while this increase was not observed in MV-treated diabetic group. In addition, the latter group showed a higher vasorelaxation in KCI-and noradrenaline-precontracted rings (P<0.05) as compared to diabetic group. Meanwhile, there was no significant difference between control and MV-treated control groups regarding relaxation response.Conclusion: It can be concluded that oral administration of MV for 2 months could improve the vasorelaxation response of the vascular system and this may prevent the development of hypertension in diabetic rats.

Objectives: Ribes biebersteinii fruit is used for treatment of hypertension in folk medicine of Azarbaijan. However it's mechanism of action is not studied. This work was aimed to examine the vasorelaxant effect of the Ribes biebersteinii fruit total extract (RBE) and role of endothelium in rat isolated aorta. Methods: Rings of aorta (3-5 mm length) were prepared and equilibrated in Krebs' solution under 2 g tension. Rings with or without endothelium were contracted by phenylephrine (PHE, 0.1mM) or PGF2a(8 mM) and then exposed to cumulative doses of RBE. In order to asses the role of endothelium in the vasorelaxant effect of RBE, tissues were studied by incubation for 20 min by (L-NAME, 100mM) or (Methylene blue, 10mM) before contraction by PHE. Results: RBE induced relaxation in rat aortic rings pre-contracted with PHE or PGF2α dose–dependently in both intact and endothelium-denuded aortic rings. The differences between the relaxant response of intact and endothelium–denuded rings were not significant (p>0.05). L-NAME and Methylene blue did not affect the RBE-induced relaxant response in rat aortic rings. Conclusion: the results indicate that RBE induces relaxation dose-dependently in rat aortic rings precontracted with PHE by a mechanism independent of endothelium function or its productions.