Effect of subchronic administration of captopril on alpha1-adrenoceptor agonist'induced contraction of isolated aorta in rat

Angiotensin II is a major endocrine hormone that affects directly both vascular smooth muscle and endothelial cells. Since vascular reactivity to angiotensin II changes in more physiological and pathophysiological conditions, the present study was performed to investigate the effect of intraperitoneal administration of angiotensin-converting enzyme inhibitor and captopril [30 and 50 mg kg 1, once daily for 8 weeks] on contractile response of rat aorta. After 8 weeks, the treated rats were anesthetized, their thoracic aortas were excised and placed in a Petri dish filled with Krebs solution for recording of contraction and relaxation response. The obtained results showed that captopril did not modify body weight gain and food or water intake but contractile response of aortic rings to phenylephrine in treated rats with 30 and 50 mg kg 1 captopril, in the presence of endothelium, decreases about 11-22% and 29-32% [P<0.05-P<0.01], respectively, when compared to the controls. Denuded aortic rings from 30 and 50 mg kg 1 captopril-treated rats showed 11-21% and 7-11% decrease in contractile response, respectively. There was a marked endothelium-dependent relaxation response to acetylcholine in 50 mg kg 1 captopril-treated rats compared to the controls [P<0.05]. Endothelium-independent relaxation response to isosorbide dinitrate showed no significant difference in all groups. According to these results, it is suggested that captopril exerts its relaxant effect directly and/or indirectly through endothelium by production and releasing of endothelium-derived relaxing factors

Effect of aqueous garlic [Allium sativum L.] extract on acetylcholine and isosorbide-induced relaxation of isolated aorta in rat

The hypotensive effect of garlic has been well-documented in human subjects and animals. Since endothelial activity regulates vascular reactivity in physiological and pathophysiological conditions, the aim of the present study was to investigate the effect of garlic on endothelium-dependent and independent relaxation of rat aorta for elucidation of mechanism of the garlic anti-hypertensive effect. Four and eight weeks after treatment with garlic extract, aortic rings were studied for relaxation response to acetylcholine and isosorbide dinitrate. The obtained results showed that endothelium-dependent relaxation response of aortic rings to acetylcholine, from rats treated with garlic for 4 and 8 weeks, increases about 5-24% and 3-27%, respectively compared to controls. But, endothelium-independent relaxation response to isosorbide showed no difference in all groups. Moreover, the relaxant effect of garlic extract was time-dependent. The obtained findings strongly suggest that garlic exerts its relaxant effect through endothelium by production and/or releasing of endothelium-derived relaxing factor

Protective effect of digoxin on impaired chronotropic responsiveness to adrenergic stimulation in cholestatic rats

Decreased cardiac responsiveness to adrenergic stimulation has been observed in cholestatic liver disease, but the cause remains unclear. Previous reports have suggested that nitric oxide overproduction might have a role in cholestasis-induced bradycardia via inhibition of L-type calcium channels. In the present study, the digoxin has been used to increase cardiac Ca2+ transient in male Sprague-Dawley rats with obstructive cholestasis and the chronotropic responsiveness to adrenergic stimulation was evaluated. Cholestasis was induced by surgical ligation of the bile duct under general anesthesia and sham-operated animals were considered as control. The animals were divided into two groups, which received either digoxin [10, 20 micro g/kg/day] or saline. One week after the operation, spontaneously beating atria were isolated and chronotropic responses to epinephrine were evaluated in a standard oxygenated organ bath. The basal spontaneous beating rate of the atria in the cholestatic animals was not significantly different from that of sham-operated rats in vitro. Meanwhile, cholestasis induced a significant decrease in chronotropic effect of epinephrine. This effect was corrected by daily administration of digoxin [20 micro g/kg/day]. The results also showed that plasma alkaline phosphatase activity was increased by bile-duct ligation, and digoxin treatment had no effect in the elevation of this marker of liver damage. The protective effect of digoxin on impaired chronotropic responsiveness to adrenergic stimulation in cholestatic rats might be related to increase of Ca2+ transient. However, further studies are necessary to confirm the molecular basis of this effect