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 H₁ receptor antagonist chlorpheniramine (10⁻⁸ M) but not by the H₂ receptor antagonist cimetidine (3 × 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 × 10⁻⁵ and 10⁻⁴ M),2) bicarbonate-free HEPES solution to disable Cl⁻/HCO 3− exchanger, and 3) blockade of Cl⁻ channels with the use of niflumic acid, 5-nitro-2-(3-phenylpropylamino) benzoic acid, and indoleacetic acid 94R-(+)-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.