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J Physiol. 1997 Jul 15;502 ( Pt 2):259-64.

Chloride channel blockers inhibit myogenic tone in rat cerebral arteries.

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Department of Pharmacology, University of Vermont, Colchester 05446, USA.


1. We have investigated the role of chloride channels in pressure-induced depolarization and contraction of cerebral artery smooth muscle cells. 2. Two chloride channel blockers, indanyloxyacetic acid (IAA-94) and 4,4'-diisothiocyanatostilbene-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. 3. 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. 4. 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.

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