Vasorelaxant effect of harman

The in vivo cardiovascular effect and in vitro vasorelaxant effect of harma n, one of harmala alkaloids isolated from Peganum harmala, were examined in this study. Harman (1-10 mg/kg, i.v.) dose-dependently produced transient hypotension and long-lasting bradycardia in pentobarbital-anesthetized rats , which were attenuated by N-G-nitro-L-arginine pretreatment. In isolated r at endothelium-intact thoracic aortic rings, barman concentration dependent ly relaxed phenylepherine-induced contractions with an IC50 value around 9 mu M. This vasorelaxant effect was attenuated by endothelium removal or N-o mega-nitro-L-arginine methyl ester pretreatment, but not by tetraethylammon ium or indomethacin pretreatment. In cultured rat aortic endothelial cells, harman (1-100 mu M) concentration dependently increased nitric oxide (NO) release, which was dependent on the presence of external Ca2+. Harman pretr eatment (3-30 mu M) also concentration dependently inhibited the contractio ns induced by phenylephrine, 5-hydroxytryptamine (5-HT), and KCl in endothe lium-denuded aortic rings in a non-competitive manner. In addition, harman pretreatment reduced both phasic and tonic phases of phenylephrine induced contractions. Receptor binding assays further indicated that harman (K-i va lues around 5-141 mu M) interacted with the cardiac alpha(1)-adrenoceptors, brain 5-HT2 receptors, and cardiac 1,4-dihydropyridine binding site of L-t ype Ca2+ channels. Therefore, the present results suggested that the vasore laxant effect of harman was attributed to its actions on the endothelial ce lls to release NO and on the vascular smooth muscles to inhibit the contrac tions induced by the activation of receptor-linked and voltage-dependent Ca 2+ channels. The vasorelaxant effect may be involved in the hypotensive eff ect of harman. (C) 2000 Elsevier Science B.V. All rights reserved.