Objective: The aim of this study was to provide evidence that peroxynitrite may differentially affect the function of arginine vasopressin (AVP) V1a 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 V1a receptors and α1-adrenoceptors in vascular smooth muscle of the rat. The possibility that peroxynitrite impairs AVP V1a receptor function by transient oxidation events whereas peroxynitrite impairs α1-adrenoceptor function by transient oxidation and permanent nitration events will be discussed.
Bibliographical noteFunding Information:
This work was supported in part by a VMES award from the Veterinary College of the University of Georgia.
- Adrenergic alpha-adrenoceptors
- Arginine vasopressin V receptors
- Blood pressure