Stereoselective actions of S-nitrosocysteine in central nervous system of conscious rats

R. L. Davisson, M. D. Travis, J. N. Bates, A. K. Johnson and S. J. Lewis Cardiovascular Center, University of Iowa, Iowa City 52242, USA. This study examined whether the stereoselective actions of S-nitrosocysteine (SNC) in the central nervous system involves the activation of stereoselective SNC recognition sites. We examined the effects produced by intracerebroventricular injection of the L- and D-isomers of SNC (L- and D-SNC) on mean arterial blood pressure, heart rate, and vascular resistances in conscious rats. We also examined the hemodynamic effects produced by intracerebroventricular injections of 1) L-cystine, the major non-nitric oxide (NO) decomposition product of L-SNC, 2) the parent thiols L- and D-cysteine, and 3) the bulky S-nitrosothiol L-S-nitroso-gamma-glutamylcysteinylglycine [L-S-nitrosoglutathione, (L-SNOG)]. Finally, we examined the decomposition of L- and D-SNC and L-SNOG to NO on their addition to brain homogenates. The intracerebroventricular injection of L-SNC (250-1,000 nmol) produced falls in mean arterial pressure, increases in heart rate, and a dose-dependent pattern of changes in hindquarter, renal, and mesenteric vascular resistances. The intracerebroventricular injections of D-SNC, L-cystine, and L-SNOG produced only minor effects. The intracerebroventricular injection of L-cysteine produced pressor responses and tachycardia, whereas D-cysteine was inactive. L- and D-SNC decomposed equally to NO on addition to brain homogenates. L-SNOG decomposed to similar amounts of NO as L- and D-SNC. These results suggest that SNC may activate stereoselective SNC recognition sites on brain neurons and that S-nitrosothiols of substantially different structure do not stimulate these sites. These recognition sites may be stereoselective membrane-bound receptors for which L-SNC is the unique ligand.