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.
Kooy
N W
NW
Cardiovascular Center, University of Iowa College of Medicine, Iowa City 52242, USA.
Lewis
S J
SJ
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009566:Nitrates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000322:Adrenergic Agonists; D009566:Nitrates; D001127:Arginine Vasopressin; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine