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

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 utilizedl-penicillamine, which attenuates the hemodynamic effects of systemically injected S-nitrosothiols. The hemodynamic effects of peroxynitrite and the S-nitrosothiolsl- S-nitrosocysteine,l- S-nitrosoglutathione, and S-nitrosoalbumin were determined before and 25 min after the administration ofl-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 byl-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.