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

NW Kooy, SJ Lewis - European journal of pharmacology, 1996 - Elsevier
NW Kooy, SJ Lewis
European journal of pharmacology, 1996Elsevier
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 μg/kg, iv, n= 6), epinephrine
(0.5–4 μg/kg, iv, n= 7), phenylephrine (1–8 μg/kg, iv, n= 5), and isoproterenol (100–400 …
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 μg/kg, i.v., n = 6), epinephrine (0.5–4 μg/kg, i.v., n = 7), phenylephrine (1–8 μg/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 μ mol/kg, i.v.) in pentobarbital-anesthetized rats. These results demonstrate substantial and selective attenuation of the hemodynamic effects produced by α- and β-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.
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