Peroxynitrite-mediated attenuation of alpha- and beta-adrenoceptor agonist-induced vascular responses in vivo

Peroxynitrite is produced by vascular endothelial and smooth muscle cells i n response to inflammation, induces vascular relaxation, and alters vascula r responses to endothelial-derived relaxing factors. The present study exam ined the changes in mean arterial pressure and hindquarter, renal, and mese nteric vascular resistances produced by the systemic administration of (i) the catecholamines epinephrine or norepinephrine, (ii) the alpha(1)-adrenoc eptor agonist phenylephrine, (iii) the P-adrenoceptor agonist isoproterenol or (iv) [Arg delta] vasopressin in pentobarbital-anesthetized rats prior t o and following the systemic administration of peroxynitrite. The systemic administration of peroxynitrite significantly inhibited (i) epinephrine-ind uced presser and renal and mesenteric vasoconstrictor responses, (ii) norep inephrine-induced presser and hindquarter, renal, and mesenteric vasoconstr ictor responses, (iii) phenylephrine-induced hindquarter and mesenteric vas oconstrictor responses, and (iv) isoproterenol-induced depressor and hindqu arter and renal vasodilator responses. In comparison, the systemic administ ration of peroxynitrite had no effect on arginine vasopressin-induced press er or vasoconstrictor responses. These results demonstrate selective and co nsequential attenuation of the hemodynamic effects produced by alpha- and b eta-adrenoceptor agonists, suggesting that selective impairment of adrenoce ptors by peroxynitrite may play a critical role in the hemodynamic dysfunct ion associated with inflammatory conditions. (C) 1999 Elsevier Science B.V. All rights reserved.