Differential effects of peroxynitrite on the function of arginine vasopressin V(1a) receptors and alpha(1)-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 alpha(1)-adrenoceptors in vascular smooth muscle of the rat


METHODS
The vasoconstrictor responses elicited by AVP, or the alpha(1)-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 alpha(1)-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 alpha(1)-adrenoceptor function by transient oxidation and permanent nitration events will be discussed.
Lewis
Stephen J
SJ
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389, USA. slewis@vet.uga.edu
Hoque
Azizul
A
Sandock
Kevin
K
Robertson
Tom P
TP
Bates
James N
JN
Kooy
Neil W
NW
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D006902:Hydroxymercuribenzoates / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009580:Nitroblue Tetrazolium / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000187:drug effects* / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D006902:Hydroxymercuribenzoates; D009566:Nitrates; D018340:Receptors, Adrenergic, alpha-1; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C030601:4-hydroxymercuribenzoate; D030421:Peroxynitrous Acid; D010656:Phenylephrine; D009580:Nitroblue Tetrazolium; D005978:Glutathione