title: Suppression of peripheral sympathetic activity underlies protease-activated receptor 2-mediated hypotension.
abstract: Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ω-conotoxin GVIA (CgTx), a selective N-type Ca(2+) channel (ICa-N) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Duck-Sun
authors.initials: DS
authors.lastname: Ahn
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Joeng
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Seungsoo
authors.initials: S
authors.lastname: Chung
keywords: Hypotension; Mesenteric artery; N-type Ca2+ channel; Peripheral sympathetic output; Protease-activated receptor 2