CHLORIDE CHANNEL BLOCKERS INHIBIT MYOGENIC TONE IN RAT CEREBRAL-ARTERIES

1. We have investigated the role of chloride channels in pressure-indu ced depolarization and contraction of cerebral artery smooth muscle ce lls. 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 pressuri zed (80 mmHg), rat posterior cerebral arteries. Niflumic acid, a block er of calcium-activated chloride channels, diet not affect arterial to ne. 3. Dilatations to IAA-94 and DIDS were unaffected by potassium cha nnel blockers, but were prevented by elevated potassium. IAA-94 and DI DS had no effect on membrane potential or diameter of arteries at low intravascular pressure, where myogenic tone is absent. Reduction of ex tracellular chloride (80 mM Cl-) increased the pressure-induced contra ctions. Removal of extracellular sodium did not affect the pressure-in duced responses. 4. Our results suggest that intravascular pressure ac tivates DIDS- and IAA-94-sensitive chloride channels to depolarize art erial smooth muscle, thereby contributing to the myogenic constriction .