Manipulation of chloride flux affects histamine-induced contraction in rabbit basilar artery

Cl- efflux induces depolarization and contraction of smooth muscle cells. This study was undertaken to explore the role of Cl- flux in histamine-induced contraction in the rabbit basilar artery. Male New Zealand White rabbits (n = 16) weighing 1.8-2.5 kg were euthanized by an overdose of pentobarbital sodium. The basilar arteries were removed for isometric tension recording. Histamine produced a concentration-dependent contraction that was attenuated by the H-1 receptor antagonist chlorpheniramine (10(-8) M) but not by the H-2 receptor antagonist cimetidine (3 X 10(-6) M) in normal Cl- Krebs-Henseleit bicarbonate solution (123 mM Cl-). The histamine-induced contraction was reduced by the following manipulations: 1) inhibition of Na+-K+-2Cl(-) cotransporter with bumetanide (3 x 10(-5) and 10(-4) M), 2) bicarbonate-free HEPES solution to disable Cl-/HCO3- exchanger, and 3) blockade of Cl- channels with the use of niflumic acid, 5-nitro-2-(3-phenylpropylamino) benzoic acid, and indoleacetic acid 94 R-(+)-methylindazone. In addition, substitution of extracellular Cl- (10 mM) with methanesulfonate acid (113 mM) transiently enhanced histamine-induced contraction. Manipulation of Cl- flux affects histamine-induced contraction in the rabbit basilar artery.