Location and function of VPAC1, VPAC2 and NPR-C receptors in VIP-induced vasodilation of porcine basilar arteries.
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.
Grant
Stuart
S
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, UK.
Lutz
Eve M
EM
McPhaden
Alan R
AR
Wadsworth
Roger M
RM
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects / Q000502:physiology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C