@article{APS6590,
author = {Cui Yang and Yiu-wa Kwan and Shun-wan Chan and Simon Ming-yuen Lee and George Pak-heng Leung},
title = {Potentiation of EDHF-mediated relaxation by chloride channel blockers},
journal = {Acta Pharmacologica Sinica},
volume = {31},
number = {10},
year = {2016},
keywords = {},
abstract = {Aim: To investigate the involvement of Cl− channels in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in rat mesenteric arteries.
Methods: Cl− channel and Kir channel activities were studied using whole-cell patch clamping in rat mesenteric arterial smooth muscle cells. Isometric tension of arterial rings was measured in organ chambers.
Results: The volume-activated Cl− current in rat mesenteric arterial smooth muscle cells was abolished by Cl− channel blockers NPPB or DIDS. The EDHF-mediated vasorelaxation was potentiated by NPPB and DIDS. The EDHF response was diminished by a combination of apamin and charybdotoxin, which agreed with the hypothesis that EDHF response involves the release of K+ via the Ca2+-activated K+ channels in endothelial cells. The elevation of K+ concentration in bathing solution from 1.2 mmol/L to 11.2 mmol/L induced an arterial relaxation, which was abolished by the combination of BaCl2 and ouabain. It is consistent to the hypothesis that K+ activates K+/Na+-ATPase and inward rectifier K+ (Kir) channels, leading to the hyperpolarization and relaxation of vascular smooth muscle. The K+-induced relaxation was augmented by NPPB, DIDS, or withdrawal of Cl− from the bathing solution, which could be reversed by BaCl2, but not ouabain. The potentiating effect of Cl− channel blockers on K+-induced relaxation was probably due to the interaction between Cl− channels and Kir channels. Moreover, the K+-induced relaxation was potentiated when the arteries were incubated in hyperosmotic solution, which is known to inhibit volume-activated Cl− channels.
Conclusion: The inhibition of Cl− channels, particularly the volume-activated Cl− channels, may potentiate the EDHF-induced vasorelaxation through the Kir channels.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6590}
}