HEMODYNAMIC-EFFECTS OF L-S-NITROSO-BETA,BETA-DIMETHYLCYSTEINE AND D-S-NITROSO-BETA,BETA-DIMETHYLCYSTEINE IN RATS

This study examined whether S-nitroso-beta,beta-dimethylcysteine (S-ni trosopenicillamine; SNPEN) may activate stereoselective S-nitrosothiol receptors within the vasculature. We examined 1) the hemodynamic effe cts produced by the L-and D-isomers of SNPEN (12.5-400 nmol/kg iv), th e L-and D-isomers of the parent thiols [L-and D-penicillamine (PEN); 1 2.5-400 nmol/kg iv], and the nitric oxide (NO) donor sodium nitropruss ide (SNP; 1-10 mu g/kg iv) in conscious rats; 2) the hemodynamic effec ts produced by these compounds in urethan-anesthetized rats; and 3) th e relative decomposition of L-and D-SNPEN to NO on addition to rat blo od or cultured porcine aortic smooth muscle (PASM) cells. We found tha t 1) L-SNPEN was a more potent hypotensive and vasodilator agent withi n the mesenteric bed and within sympathetically intact and sympathetic ally denervated hindlimb beds of conscious rats than was D-SNPEN; 2) t he hypotension and vasodilation produced by L-SNPEN was similar in con scious and anesthetized rats, whereas the effects of D-SNPEN and SNP w ere augmented by urethan-anesthesia; 3) L-and D-PEN did not affect hem odynamic parameters in conscious or anesthetized rats; and 4) Land D-S NPEN decomposed equally to NO on addition to rat blood or PASM cells. These results suggest that the vasodilator effects of SNPEN involve th e interaction of this S-nitrosothiol with stereoselective recognition sites within the vasculature and that urethan alters the mechanisms by which L-and D-SNPEN relax vascular smooth muscle.