Chloride channel blockers inhibit myogenic tone in rat cerebral arteries.
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.
Nelson
M T
MT
Department of Pharmacology, University of Vermont, Colchester 05446, USA.
Conway
M A
MA
Knot
H J
HJ
Brayden
J E
JE
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D004232:Diuretics / Q000494:pharmacology; D006016:Glycolates / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014664:Vasodilation
D018118:Chloride Channels; D004232:Diuretics; D006016:Glycolates; C015765:MK 473; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium