HEMODYNAMIC-EFFECTS OF L-S-NITROSOCYSTEINE AND D-S-NITROSOCYSTEINE INTHE RAT - STEREOSELECTIVE S-NITROSOTHIOL RECOGNITION SITES

The vasorelaxant effects of the endothelium-derived relaxing factor S- nitrosocysteine (SNC) may not be simply due to its decomposition to NO . The biological actions of SNC may also involve the transnitrosation of amino acids in the blood and in plasma membranes. The possibility t hat the SNC moiety possesses biological activity prompted us to examin e whether the hemodynamic effects of this S-nitrosothiol involves the activation of stereoselective S-nitrosothiol receptors within the card iovascular system. We examined (1) the hemodynamic effects produced by intravenous injections of the L and D isomers of SNC (L- and D-SNC, r espectively; 100 to 800 nmol/kg), the L and D isomers of the parent th iols (L- and D-cysteine, respectively; 100 to 800 nmol/kg), the oxidiz ed thiol L-cystine (100 to 800 nmol/kg), and the NO donor sodium nitro prusside (SNP, 1 to 36 mu g/kg) in conscious freely moving rats, (2) t he baroreceptor reflex-mediated changes in heart rate elicited in resp onse to the falls in arterial pressure produced by L- and D-SNC and SN P in conscious rats, and (3) the relative decomposition of L- and D-SN C to NO upon addition to heparinized rat blood or upon direct applicat ion to cultured porcine aortic smooth muscle (PASM) cells. We now repo rt that (1) L-SNC is a more potent hypotensive and vasodilator agent w ithin the mesenteric bed and sympathetically intact and sympatheticall y denervated hindlimb beds of conscious rats than is D-SNC, (2) L- and D-SNC markedly inhibit baroreceptor reflex-mediated tachycardia in co nscious rats and D-SNC is considerably more effective than L-SNC, (3) the intravenous injections of L- and D-cysteine or L-cystine do not af fect arterial blood pressure or vascular resistances, and (4) L- and D -SNC decompose equally to NO upon application to rat blood or cultured PASM cells. These results suggest that the hemodynamic effects of end ogenous SNC may involve its interaction with stereoselective S-nitroso thiol recognition sites within the vasculature and the baroreflex are. These findings provide tentative evidence that membrane-bound S-nitro sothiol receptors may exist within the cardiovascular system.