Suppression of Peripheral Sympathetic Activity Underlies Protease-Activated Receptor 2-Mediated Hypotension.
10.4196/kjpp.2014.18.6.489
- Author:
Young Hwan KIM
1
;
Duck Sun AHN
;
Ji Hyun JOENG
;
Seungsoo CHUNG
Author Information
1. Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea. sschung@yuhs.ac
- Publication Type:Original Article
- Keywords:
Hypotension;
Mesenteric artery;
N-type Ca2+ channel;
Peripheral sympathetic output;
Protease-activated receptor 2
- MeSH:
Animals;
Blood Pressure;
Endothelial Cells;
Hypotension*;
Mesenteric Arteries;
Mesenteric Artery, Superior;
Muscle, Smooth;
Muscle, Smooth, Vascular;
Norepinephrine;
omega-Conotoxin GVIA;
Rats;
Receptor, PAR-2;
Thrombin
- From:The Korean Journal of Physiology and Pharmacology
2014;18(6):489-495
- CountryRepublic of Korea
- Language:English
-
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, omega-conotoxin GVIA (CgTx), a selective N-type Ca2+ channel (I(Ca-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 omega-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of I(Ca-N) which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.
