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Am J Physiol Heart Circ Physiol 274: H1001-H1008, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 3, H1001-H1008, March 1998

Peroxynitrite-mediated vasorelaxation: evidence against the formation of circulating S-nitrosothiols

Jonathan E. Graves1, Stephen J. Lewis2, and Neil W. Kooy1

Departments of 1 Pediatrics and 2 Pharmacology, The University of Iowa, Iowa City, Iowa 52242

Peroxynitrite-induced relaxation of isolated vessels may involve the formation of S-nitrosothiols. This study characterized the hemodynamic effects of systemically injected peroxynitrite in pentobarbital sodium-anesthetized rats and determined whether these effects were due to the formation of S-nitrosothiols. We utilized L-penicillamine, which attenuates the hemodynamic effects of systemically injected S-nitrosothiols. The hemodynamic effects of peroxynitrite and the S-nitrosothiols L-S-nitrosocysteine, L-S-nitrosoglutathione, and S-nitrosoalbumin were determined before and 25 min after the administration of L-penicillamine or saline. Peroxynitrite and the S-nitrosothiols produced dose-dependent reductions in mean arterial pressure and mesenteric and hindquarter vascular resistances. The hypotensive and vasodilator effects of the S-nitrosothiols were significantly reduced by L-penicillamine. In contrast, the hemodynamic actions of peroxynitrite were unaffected by L-penicillamine. Therefore, peroxynitrite produces hypotensive and vasodilator responses in anesthetized rats that are unlikely to be due to the formation of circulating S-nitrosothiols. The mechanisms by which peroxynitrite produces vasodilatation in vivo remain to be determined.

nitric oxide; S-nitrosocysteine; S-nitrosoglutathione; S-nitrosoalbumin; vasodilatation


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