The effects of the peroxynitrite product nitrotyrosine on the hemodynamic responses produced by nitrosyl factors in the rat

J. A. Royall, S. J. Lewis, N. W. Kooy

Research output: Contribution to journalArticle

Abstract

Peroxynitrite is formed endogenously by the near diffusion-limited reaction of nitric oxide with Superoxide anion. Peroxynitrite nitrates free and proteinassociated tyrosine residues to specifically form 3-nitro-L-tyrosine (NT). We have shown that NT is a potent inhibitor of the vasoconstrictor effects of norepinephrine, the selective ai-adrenoceptor agonist phenylephrine, and angiotensin II. These findings would predict that NT should produce hypotension via dilation of resistance vessels. However, NT-treated rats display normal blood pressure and vascular resistances. This observation prompted us to examine whether NT interferes with the biological potency of endogenously-derived vasodilating nitrosyl factors. We examined the hemodynamic effects of the L- and D-isomers of the putative endotheliumderived relaxing factor S-nitrosocysteine (L- and D-SNC, 25-200 nmol/kg, i.v.) prior to and following the administration of NT (2.5 p,mol/kg, i.v.) in pentobarbital (50 mg/kg, i.p.)-anesthetized rats. The administration of NT did not affect baseline mean arterial pressure, or hindquarter, renal, or mesenteric vascular resistances. The hindquarter vasodilator effects of L-SNC were substantially diminished 15 to 30 minutes following the administration of NT. The hypotensive and vasodilator effects of D-SNC were unchanged. The hypotensive and hindquarter vasodilator effects of L-SNC were also substantially diminished 45 to 75 minutes following the administration of NT. Again, the hemodynamic effects of D-SNC were unchanged. These studies demonstrate that NT attenuates the hindquarter vasodilator responses produced by L-SNC but not D-SNC. These results suggest that NT or a secondary metabolite interferes with the binding of L-SNC to a stereoselective recognition site in the vasculature of the hindlimb of the rat.

Original languageEnglish (US)
Pages (from-to)A569
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

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