Comparative study on the vasorelaxant effects of three harmala alkaloids in vitro

Three psychological active principles from the seeds of Peganum harmala L., harmine, harmaline and harmalol, showed vasorelaxant activities in isolate d rat thoracic aorta preparations precontracted by phenylephrine or KCl wit h rank order of relaxation potency of harmine > harmaline > harmalol. The v asorelaxant effects of harmine and harmaline (but not harmalol) were attenu ated by endothelium removal or pretreatment with a nitric oxide (NO) syntha se N-omega-nitro-L-arginine methyl ester. In cultured rat aortic endothelia l cells, harmine and harmaline (but not harmalol) increased NO release, whi ch was dependent on the presence of external Ca2+. In endothelium-denuded p reparations, pretreatment of harmine, harmaline or harmalol (3 - 30 muM) in hibited phenylephrine-induced contractions in a non-competitive manner. Rec eptor binding assays indicated that all 3 compounds interacted with cardiac alpha (1)-adrenoceptors with comparable affinities (K-i value around 31 - 36 muM), but only harmine weakly interacted with the cardiac 1,4-dihydropyr idine binding site of L-type Ca2+ channels (K-i value of 408 muM). Therefor e, the present results suggested that the vasorelaxant effects of harmine a nd harmaline are attributed to their actions on the endothelial cells to re lease NO and on the vascular smooth muscles to inhibit the contractions ind uced by the activation of receptor-linked and voltage-dependent Ca2+ channe ls. The vasorelaxant effect of harmalol was not endothelium-dependent.