NITROTYROSINE ATTENUATES THE HEMODYNAMIC-EFFECTS OF ADRENOCEPTOR AGONISTS IN-VIVO - RELEVANCE TO THE PATHOPHYSIOLOGY OF PEROXYNITRITE

Peroxynitrite, which attenuates catecholamine-mediated hemodynamic res ponses in vivo, nitrates free tyrosine residues to form the specific p roduct, 3-nitro-L-tyrosine. The chemical structure of 3-nitro-L-tyrosi ne is similar to that of the endogenous catecholamines. Therefore, 3-n itro-L-tyrosine may interfere with catecholamine hemodynamic function in vivo. The hemodynamic responses produced by norepinephrine (1-4 mu g/kg, i.v., n=6), epinephrine (0.5-4 mu g/kg, i.v., n=7), phenylephrin e (1-8 mu g/kg, i.v., n=5); and isoproterenol (100-400 ng/kg, i.v., n= 5) were attenuated, while the hemodynamic responses produced by argini ne vasopressin (50-250 ng/kg; i.v., n=5) were unaffected following the administration of 3-nitro-L-tyrosine (2.5 mu mol/kg, i.v.) in pentoba rbital-anesthetized rats. These results demonstrate substantial and se lective attenuation of the hemodynamic effects produced by alpha- and beta-adrenoceptor agonists, raising the possibility that S-nitro-L-tyr osine may play a role in the hemodynamic dysfunction associated with i nflammatory conditions in which the formation of peroxynitrite is favo red.