1. ¹Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, UK
2. ²Department of Bioscience, University of Strathclyde, Glasgow, Scotland, UK
3. ³Department of Pathology, Glasgow Royal Infirmary, Glasgow, Scotland, UK

Correspondence: Professor RM Wadsworth, Department of Physiology and Pharmacology, University of Strathclyde, 27 Taylor Street, Glasgow, Scotland G4 0NR, UK. E-mail: r.m.wadsworth@strath.ac.uk

Received 13 January 2005; Revised 7 March 2005; Accepted 18 April 2005; Published online 15 June 2005.

Abstract

Vasoactive intestinal peptide (VIP) is a vasodilator peptide present in cerebrovascular nerves. Vasoactive intestinal peptide can activate VPAC₁, VPAC₂ 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 VPAC₁ receptor is expressed on the endothelium, VPAC₂ 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 VPAC₁ receptor agonist was inhibited by L-NAME and abolished by endothelial denudation. Vasodilation induced by Ro-25–1553, the VPAC₂ 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 VPAC₂ antagonist. This study shows that all known VIP receptors are involved in VIP-mediated vasodilation of porcine basilar arteries. The VPAC₁ receptor is located on the endothelium and elicits vasodilation by generating nitric oxide (NO). The VPAC₂ 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.