Differential effects of peroxynitrite on the function of arginine vasopressin V_1a receptors and alpha₁-adrenoceptors in vivo

Objective: The aim of this study was to provide evidence that peroxynitrite may differentially affect the function of arginine vasopressin (AVP) V_1a receptors and α₁-adrenoceptors in vascular smooth muscle of the rat. Methods: The vasoconstrictor responses elicited by AVP, or the α₁-adrenoceptor agonist, phenylephrine, were determined in anesthetized rats before and after injections of (i) peroxynitrite, the thiol chelator, para-hydroxymercurobenzoic acid (PHMBA), or the electron acceptor, nitroblue tetrazolium (NBT). The ability of the reducing agent, glutathione, to reverse the loss of response to phenylephrine and AVP in peroxynitrite-treated rats was also examined. Results: The AVP-induced responses were suppressed 10-20 min but not 60-70 min after the administration of peroxynitrite. Glutathione reversed the above loss of response to AVP at 10-20 min. The responses elicited by phenylephrine were suppressed 10-20 min and 60-70 min after administration of peroxynitrite. Glutathione did not reverse the above losses of response to phenylephrine. In addition, the vasoconstrictor actions of AVP and phenylephrine were markedly suppressed after administration of PHMBA or nitroblue tetrazolium. Conclusions: The above findings provide evidence that exogenously administered peroxynitrite may differentially affect the function of AVP V_1a receptors and α₁-adrenoceptors in vascular smooth muscle of the rat. The possibility that peroxynitrite impairs AVP V_1a receptor function by transient oxidation events whereas peroxynitrite impairs α₁-adrenoceptor function by transient oxidation and permanent nitration events will be discussed.