Potentiation of EDHF-mediated relaxation by chloride channel blockers

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Journal Article

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Endothelium-derived hyperpolarizing factor, Chloride channels, Potassium channels




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.

Source Publication

Acta Pharmacologica Sinica

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