Chloride efflux is involved in ET-1 and 5-HT-induced contraction in rabbit basilar artery

Chloride (Cl^-) efflux induces depolarization and contributes to contraction of cerebral arteries. We tested the effect of endothelin-1 and 5-hydroxytryptamine on isometric tension in rabbit basilar artery by inhibition of Na⁺-K⁺-2Cl^- co-transporter and Cl ^-/HCO₃^- exchanger to decrease Cl^-, by decreasing extracellular Cl^- concentration, and by blocking Cl^- channels using Cl^- channel inhibitors. We have made the following observations: (i) endothelin-1 and 5-hydroxytryptamine produced contraction in the normal Cl^- Krebs-Henseleit bicarbonate solution (123 mM Cl^-); (ii) inhibition of Na⁺-K⁺- 2Cl^- co-transporter with bumetanide abolished the contractions; (iii) bicarbonate-free solution with HEPES reduced contractions to 5-hydroxytryptamine and endothelin-1; (iv) substitution of extracellular Cl ^- with methanesulfonate acid (MS^- 113 mM, Cl^- 10 mM) enhanced peak contraction to 5-hydroxytryptamine and endothelin-1 and decreased plateau contraction to 5-hydroxytryptamine, but did not affect the plateau contraction to endothelin-1 and KCl; and (v) blockade of Ca ²⁺-dependent Cl^- channel with niflumic acid and non-selective Cl^- channel with 5-nitro-2-(3-phenylpropylamino) benzoic acid and indanyloxyacetic acid-94, R- (+)-methylindazone (R- (+)-IAA-94) decreased contractions to endothelin-1 and 5-hydroxytryptamine. However, removal of endothelium attenuated the effect of Cl^- channel inhibitors. In conclusion, Cl^- channels and Cl^- flux are involved in endothelin-1-induced and 5-hydroxytryptamine-induced contraction in rabbit basilar artery. Cl^- channel blockers might exert additional effects by releasing vasodilatation agents from endothelial cells.