Hemodynamic effects of L- and D-S-nitroso-beta,beta-dimethylcysteine in rats.
This study examined whether S-nitroso-beta,beta-dimethylcysteine (S-nitrosopenicillamine; SNPEN) may activate stereoselective S-nitrosothiol receptors within the vasculature. We examined 1) the hemodynamic effects produced by the L- and D-isomers of SNPEN (12.5-400 nmol/kg iv), the L- and D-isomers of the parent thiols [L- and D-penicillamine (PEN); 12.5-400 nmol/kg iv], and the nitric oxide (NO) donor sodium nitroprusside (SNP; 1-10 micrograms/kg iv) in conscious rats; 2) the hemodynamic effects produced by these compounds in urethan-anesthetized rats; and 3) the relative decomposition of L- and D-SNPEN to NO on addition to rat blood or cultured porcine aortic smooth muscle (PASM) cells. We found that 1) L-SNPEN was a more potent hypotensive and vasodilator agent within the mesenteric bed and within sympathetically intact and sympathetically denervated hindlimb beds of conscious rats than was D-SNPEN; 2) the hypotension and vasodilation produced by L-SNPEN was similar in conscious and anesthetized rats, whereas the effects of D-SNPEN and SNP were augmented by urethan-anesthesia; 3) L- and D-PEN did not affect hemodynamic parameters in conscious or anesthetized rats; and 4) L- and D-SNPEN decomposed equally to NO on addition to rat blood or PASM cells. These results suggest that the vasodilator effects of SNPEN involve the 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.
Travis
M D
MD
Cardiovascular Center, University of Iowa, Iowa City 52242, USA.
Davisson
R L
RL
Bates
J N
JN
Lewis
S J
SJ
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D003714:Denervation; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply / Q000294:innervation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D013237:Stereoisomerism; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
C105567:S-nitroso-dimethylcysteine; D009599:Nitroprusside; D010396:Penicillamine