Nitrotyrosine attenuates the hemodynamic effects of adrenoceptor agonists in vivo: relevance to the pathophysiology of peroxynitrite.

Peroxynitrite, which attenuates catecholamine-mediated hemodynamic responses in vivo, nitrates free tyrosine residues to form the specific product, 3-nitro-L-tyrosine. The chemical structure of 3-nitro-L-tyrosine is similar to that of the endogenous catecholamines. Therefore, 3-nitro-L-tyrosine may interfere with catecholamine hemodynamic function in vivo. The hemodynamic responses produced by norepinephrine (1-4 micrograms/kg, i.v., n = 6), epinephrine (0.5-4 micrograms/kg, i.v., n = 7), phenylephrine (1-8 micrograms/kg, i.v., n = 5), and isoproterenol (100-400 ng/kg, i.v., n = 5) were attenuated, while the hemodynamic responses produced by arginine vasopressin (50-250 ng/kg; i.v., n = 5) were unaffected following the administration of 3-nitro-L-tyrosine (2.5 mumol/kg, i.v.) in pentobarbital-anesthetized rats. These results demonstrate substantial and selective attenuation of the hemodynamic effects produced by alpha- and beta-adrenoceptor agonists, raising the possibility that 3-nitro-L-tyrosine may play a role in the hemodynamic dysfunction associated with inflammatory conditions in which the formation of peroxynitrite is favored.