Location and Function of VPAC 1 , VPAC 2 and NPR-C Receptors in VIP-Induced Vasodilation of Porcine Basilar Arteries

• Published in: Journal of cerebral blood flow and metabolism 2006-01, Vol.26 (1), p.58-67
• Main Authors: Grant, Stuart, Lutz, Eve M, McPhaden, Alan R, Wadsworth, Roger M
• Format: Article
• Language: English
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/sj.jcbfm.9600163

Vasoactive intestinal peptide (VIP) is a vasodilator peptide present in cerebrovascular nerves. Vasoactive intestinal peptide can activate VPAC 1 , VPAC 2 and the NPR-C receptor. This study sought to determine the receptors involved in VIP-induced vasodilation of porcine basilar arteries. Porcine basilar arteries contained the messenger ribonucleic acid of all three receptors. Immunocytochemical analysis of porcine basilar arteries revealed that the VPAC 1 receptor is expressed on the endothelium, VPAC 2 on the outer layers of the media and the NPR-C receptor throughout the artery, including nerves. Vasodilator responses to all receptor agonists showed that the receptors are functional. The vasodilator response to the VPAC 1 receptor agonist was inhibited by l-NAME and abolished by endothelial denudation. Vasodilation induced by Ro-25–1553, the VPAC 2 agonist, was unaffected by NOS inhibition or removal of the endothelium. Activation of the NPR-C receptor produced a vasodilation, which was susceptible to NOS inhibition and independent of endothelium. The vasodilator response to electrical stimulation at 20 Hz was attenuated by PG-99–465, the VPAC 2 antagonist. This study shows that all known VIP receptors are involved in VIP-mediated vasodilation of porcine basilar arteries. The VPAC 1 receptor is located on the endothelium and elicits vasodilation by generating nitric oxide (NO). The VPAC 2 receptor is mainly expressed in the outer layers of the smooth muscle and induces vasodilation independently of NO in response to VIP released from intramural nerves. The NPR-C receptor produces NO-dependent vasodilation independently of the endothelium by stimulation of nNOS in intramural nerves.