Hemodynamic Effects of L- and D-S-nitrosocysteine in the 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 that the SNC moiety possesses biological activity prompted us to examine whether the hemodynamic effects of this S-nitrosothiol involves the activation of stereoselective S-nitrosothiol receptors within the cardiovascular system. We examined (1) the hemodynamic effects produced by intravenous injections of the L and D isomers of SNC (L- and D-SNC, respectively; 100 to 800 nmol/kg), the L and D isomers of the parent thiols (L- and D-cysteine, respectively; 100 to 800 nmol/kg), the oxidized thiol L-cystine (100 to 800 nmol/kg), and the NO donor sodium nitroprusside (SNP, 1 to 36 micrograms/kg) in conscious freely moving rats, (2) the baroreceptor reflex-mediated changes in heart rate elicited in response to the falls in arterial pressure produced by L- and D-SNC and SNP in conscious rats, and (3) the relative decomposition of L- and D-SNC to NO upon addition to heparinized rat blood or upon direct application to cultured porcine aortic smooth muscle (PASM) cells. We now report that (1) L-SNC is a more potent hypotensive and vasodilator agent within the mesenteric bed and sympathetically intact and sympathetically denervated hindlimb beds of conscious rats than is D-SNC, (2) L- and D-SNC markedly inhibit baroreceptor reflex-mediated tachycardia in conscious 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 affect 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 endogenous SNC may involve its interaction with stereoselective S-nitrosothiol recognition sites within the vasculature and the baroreflex arc. These findings provide tentative evidence that membrane-bound S-nitrosothiol receptors may exist within the cardiovascular system.