Chloride channel blockers inhibit myogenic tone in rat cerebral arteries

Abstract

We have investigated the role of chloride channels in pressure‐induced depolarization and contraction of cerebral artery smooth muscle cells. Two chloride channel blockers, indanyloxyacetic acid (IAA‐94) and 4,4′‐diisothiocyanato‐stilbene‐2,2′‐disulphonic acid (DIDS), caused hyperpolarizations (10–15 mV) and dilatations (up to 90 %) of pressurized (80 mmHg), rat posterior cerebral arteries. Niflumic acid, a blocker of calcium‐activated chloride channels, did not affect arterial tone. Dilatations to IAA‐94 and DIDS were unaffected by potassium channel blockers, but were prevented by elevated potassium. IAA‐94 and DIDS had no effect on membrane potential or diameter of arteries at low intravascular pressure, where myogenic tone is absent. Reduction of extracellular chloride (60 mm Cl−) increased the pressure‐induced contractions. Removal of extracellular sodium did not affect the pressure‐induced responses. Our results suggest that intravascular pressure activates DIDS‐ and IAA‐94‐sensitive chloride channels to depolarize arterial smooth muscle, thereby contributing to the myogenic constriction.