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

Abstract

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[Formula: see text] 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.