Location and function of VPAC1, VPAC2 and NPR-C receptors in VIP-induced vasodilation of porcine basilar arteries
Location and function of VPAC1, VPAC2 and NPR-C receptors in VIP-induced vasodilation of porcine basilar arteries
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DOI：
10.1038/sj.jcbfm.9600163
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发表时间：
2006-01-01
影响因子：
6.3
通讯作者：
Wadsworth, RM
中科院分区：
文献类型：
--
作者：
Grant, S;Lutz, EM;Wadsworth, RM
血管活性肠肽（VIP）是存在于脑血管神经中的一种血管扩张肽。血管活性肠肽可激活VPAC（1）、VPAC（2）和NPR-C受体。本研究旨在确定VIP诱导的猪基底动脉血管舒张中涉及的受体。猪的基底动脉含有所有三种受体的信使核糖核酸。猪基底动脉的免疫细胞化学分析显示，VPAC（1）受体表达于内皮，VPAC（2）受体表达于中膜外层，NPR-C受体表达于整个动脉，包括神经。对所有受体激动剂的血管舒张反应表明受体是功能性的。对VPAC（1）受体激动剂的血管舒张反应被L-NAME抑制，并被内皮剥脱所消除。VPAC（2）激动剂Ro-25-1553诱导的血管舒张不受NOS抑制或内皮去除的影响。NPR-C受体的激活产生了血管舒张，这是敏感的NOS抑制和独立的内皮。VPAC（2）拮抗剂PG-99-465可减弱20 Hz电刺激引起的血管舒张反应。这项研究表明，所有已知的VIP受体参与VIP介导的猪基底动脉血管舒张。VPAC（1）受体位于内皮上，通过产生一氧化氮（NO）来促进血管舒张。VPAC（2）受体主要在平滑肌的外层表达，并响应于从壁内神经释放的VIP而不依赖于NO诱导血管舒张。NPR-C受体通过刺激壁内神经中的nNOS产生不依赖于内皮的NO依赖性血管舒张。
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.