Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
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J. Physiol. Pharmacol. · Dec 2002
No-dependent vasodilation induced by nebivolol in coronary circulation is not mediated by beta-adrenoceptors or by 5 HT1A-receptors.
Nebivolol is a unique beta1-adrenoceptor antagonist which possesses peripheral vasodilator properties dependent on endothelial NO. Nebivolol-induced release of NO was attributed to its L stereoisomer and to its ability to stimulate endothelial beta2, beta3 adrenoceptors or 5-HT1A receptors. Here, in the isolated guinea pig heart we analysed coronary vasodilator potency of L- and D-nebivolol and a possible role of beta2, beta3 adrenoceptors and 5-HT1A receptors in nebivolol-induced vasodilation. ⋯ The nonselective beta1/beta2-adrenoceptor antagonist--nadolol (10(-5) M), the selective beta3-adrenoceptor antagonist--L 748337 (10(-6) M) and the 5 HT1A receptor antagonist--NAN 190 (5 x 10(-6) M), none of them inhibited coronary vasodilation induced by D- and L-nebivolol. In summary, in the isolated guinea pig heart both D- and L-nebivolol act as coronary vasodilators. Coronary vasodilation induced by stereoisomers of nebivolol is mediated by endothelium-derived NO and does not depend on beta2, beta3 adrenoceptors or 5 HT1A receptors.
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J. Physiol. Pharmacol. · Dec 2002
A novel, potent and selective inhibitor of the activity of inducible nitric oxide synthase (GW274150) reduces the organ injury in hemorrhagic shock.
An enhanced formation of nitric oxide (NO) by the inducible NO synthase (iNOS) may contribute to the pathophysiology of hemorrhagic shock. This study investigates the effect of a novel, potent and selective inhibitor of iNOS activity (GW274150) on the circulatory failure and the organ injury and dysfunction associated with hemorrhagic shock in the anesthetised rat. ⋯ Interestingly, GW274150 did not reduce the delayed fall in blood pressure associated with hemorrhagic shock. We propose that an enhanced formation of NO from iNOS contributes to the organ injury and dysfunction in hemorrhagic shock, and that highly selective inhibitors of iNOS activity, such as GW274150, may represent a novel therapeutic approach for the therapy of hemorrhagic shock.