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The peroxynitrite product 3-nitro-L-tyrosine attenuates the hemodynamic responses to angiotensin II in vivo.

Abstract：

:Peroxynitrite is a potent oxidant formed endogenously by the near diffusion-limited reaction of nitric oxide with superoxide anion. Peroxynitrite specifically adds a nitro group to the ortho position of the phenolic ring of free and protein-associated tyrosines to form the stable product 3-nitro-L-tyrosine. Systemic administration of 3-nitro-L-tyrosine markedly inhibits the subsequent hemodynamic responses to alpha 1- and beta-adrenoceptor agonists in anesthetized rats. Angiotensin II is an important modulator of vascular tone. The vasoconstrictor effects of this hormone are known to involve the release of catecholamines from sympathetic tissues. In the present study, we examined whether 3-nitro-L-tyrosine (2.5 mumol/kg i.v.) would attenuate the hemodynamic responses produced by angiotensin II (0.1-1.0 microgram/kg i.v.). Angiotensin II produced increases in mean arterial pressure, and renal and mesenteric vascular resistances, but no changes in hindquarter vascular resistance. The pressor and renal and mesenteric vasoconstrictor responses produced by angiotensin II were significantly attenuated 30-60 min following the administration of 3-nitro-L-tyrosine. Further attenuation of these responses was evident 120-180 min following the administration of 3-nitro-L-tyrosine. The alpha 1-adrenoceptor antagonist prazosin also diminished the pressor and renal and mesenteric vasoconstrictor responses produced by angiotensin II. These results demonstrate that 3-nitro-L-tyrosine inhibits the hemodynamic responses to angiotensin II, possibly through the inhibition of alpha 1-adrenoceptor-mediated events. The effect of 3-nitro-L-tyrosine on the hemodynamic action of angiotensin II raises the possibility that 3-nitro-L-tyrosine may be involved in the pathogenesis of the hemodynamic disturbances associated with inflammatory conditions, such as atherosclerosis, ischemia-reperfusion, and sepsis, where formation of peroxynitrite is favored.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Kooy NW,Lewis SJ

doi

10.1016/s0014-2999(96)00623-1

subject

Has Abstract

pub_date

1996-11-14 00:00:00

pages

165-70

issue

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(96)00623-1

journal_volume

315

pub_type

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The peroxynitrite product 3-nitro-L-tyrosine attenuates the hemodynamic responses to angiotensin II in vivo.