@article{APS6678,
author = {Rong Zhou and Feng Chen and Qiang Li and De-yao Hu and Liang-ming Liu},
title = {Stimulation of the adenosine A3 receptor reverses vascular hyporeactivity after hemorrhagic shock in rats},
journal = {Acta Pharmacologica Sinica},
volume = {31},
number = {4},
year = {2016},
keywords = {},
abstract = {Aim: To investigate whether adenosine A3 receptors (A3AR) stimulation restore vascular reactivity after hemorrhagic shock through a ryanodine receptor (RyR)-mediated and large conductance calcium-activated potassium (BKCa) channel-dependent pathway.
Methods: Rat hemorrhagic shock model (40 mmHg) and vascular smooth muscle cell (VSMC) hypoxic model were used. The expression of A3AR was determined by Western blot and RT-PCR. The effect of A3AR stimulation on RyR-mediated Ca2+ release in VSMCs was analyzed by the Fura-3/AM loading Ca2+ imaging. The modulation of vascular reactivity to norepinephrine (NE) by A3AR stimulation was monitored by an isolated organ tension instrument.
Results: Decrease of A3AR expression is consistent with the loss of vasoreactivity to NE in hemorrhagic shock rats. The stimulation of A3AR with a selective agonist, IB-MECA, could partly but significantly restore the vasoreactivity in the rats, and this restorative effect could be counteracted by MRS1523, a selective A3AR antagonist. In hypoxic VSMCs, RyR activation by caffeine significantly evoked the rise of [Ca2+] compared with the control cells, a phenomenon closely associated with the development of vascular hyporeactivity in hemorrhagic shock rats. The stimulation of A3AR with IB-MECA significantly blocked this over activation of RyR-mediated Ca2+ release. RyR activation by caffeine and BKCa channel activation by NS1619 attenuated the restoration of vasoreactivity to NE resulting from A3AR stimulation by IB-MECA after hemorrhagic shock; this attenuation effect could be antagonized by a selective BKCachannel blocker.
Conclusion: These findings suggest that A3AR is involved in the modulation of vasoreactivity after hemorrhagic shock and that stimulation of A3AR can restore the decreased vasoreactivity to NE through a RyR-mediated, BKCachannel-dependent signal pathway.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6678}
}