Endothelium-derived and properties nitric oxide : actions

Abstract

Vascular smoth muscle relaxation in response to chemicaly diverse naturaly ocuring neurotransmitters and autacoids has ben atributed to the formation and/or release of one or more vascular endotheliumderived relaxing factors (EDRF5) distinct from prostacyclin. The chemical, biochemical, and pharmacological properties of one such EDRF resemble closely the properties of nitric oxide (NO). Thus, both arterial and venous EDRFs as wel as authentic NO cause heme-dependent activation of soluble guanylate cyclase, endothelium-independent vascular and nonvascular smoth muscle relaxation acompanied by tisue cyclic GMP formation, and inhibiton of platelet agregation and adhesion to endothelial cel surfaces. EDRF from artery vein, and freshly harvested and cultured aortic endothelial cels was recently identifed as NO or a labile nitroso species as asesed by chemical asay and bioasay. Endothelium-derived NO (EDNO) has an ultrashort half-life of 3-5 s due to spontaneous oxidation to nitrite and nitrate, both of which have only weak biological activity. EDNO can be synthesized from Larginine and posibly other basic amino acids and polypeptides, perhaps by oxidative metabolic pathways that could involve polyunsaturated faty acid-derived oxygen radicals. Inorganic nitrite could serve as both a stored precursor and an inactivation product of EDNO. EDNO and related EDRFs may serve physiological and/or pathophysiological roles in the regulation of local blod flow and platelet function.