@article{APS4480,
author = {Rong Zhou and Xiao-li Ding and Liang-ming Liu},
title = {Ryanodine receptor 2 contributes to hemorrhagic shock-induced bi-phasic vascular reactivity in rats},
journal = {Acta Pharmacologica Sinica},
volume = {35},
number = {11},
year = {2016},
keywords = {},
abstract = {Rong ZHOU*, Xiao-li DING, Liang-ming LIU
State Key Laboratory of Trauma, Burns and Combined Injury, the 2nd Department of Research Institute of Surgery, Daping Hospital, the Third Military Medical University, Chongqing 400042, China
Aim: Ryanodine receptor 2 (RyR2) is a critical component of intracellular Ca2+ signaling in vascular smooth muscle cells (VSMCs). The aim of this study was to investigate the role of RyR2 in abnormal vascular reactivity after hemorrhagic shock in rats.
Methods: SD rats were hemorrhaged and maintained mean arterial pressure (MAP) at 40 mmHg for 30 min or 2 h, and then superior mesenteric arteries (SMA) rings were prepared to measure the vascular reactivity. In other experiments, SMA rings of normal rats and rat VSMCs were exposed to a hypoxic medium for 10 min or 3 h. SMA rings of normal rats and VSMCs were transfected with siRNA against RyR2. Intracellular Ca2+ release in VSMCs was assessed using Fura-2/AM.
Results: The vascular reactivity of the SMA rings from hemorrhagic rats was significantly increased in the early stage (30 min), but decreased in the late stage (2 h) of hemorrhagic shock. Similar results were observed in the SMA rings exposed to hypoxia for 10 min or 3 h. The enhanced vascular reactivity of the SMA rings exposed to hypoxia for 10 min was partly attenuated by transfection with RyR2 siRNA, whereas the blunted vascular reactivity of the SMA rings exposed to hypoxia for 3 h was partly restored by transfection with RyR2 siRNA. Treatment with the RyR agonist caffeine (1 mmol/L) significantly increased Ca2+ release in VSMCs exposed to hypoxia for 10 min or 3 h, which was partially antagonized by transfection with RyR2 siRNA.
Conclusion: RyR2-mediated Ca2+ release contributes to the development of bi-phasic vascular reactivity induced by hemorrhagic shock or hypoxia.
Keywords: hemorrhagic shock; hypoxia; vascular reactivity; artery ring; vascular smooth muscle cell; RyR2; Ca2+; caffeine; siRNA
This project was supported by National Natural Science Foundation of China (No 81100227 and 81370427) and the Key Project of Natural Science Foundation of Chongqing (No 2010BC5126).
* To whom correspondence should be addressed.
E-mail zhourong200012@163.com
Received 2014-02-24 Accepted 2014-06-05},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4480}
}