endothelin-1 and methanesulfonic-acid

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 Ca2+-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.

Topics: Animals; Basilar Artery; Bumetanide; Chloride Channels; Chloride-Bicarbonate Antiporters; Chlorides; Dose-Response Relationship, Drug; Endothelin-1; Endothelium, Vascular; Glycolates; In Vitro Techniques; Male; Mesylates; Niflumic Acid; Nitrobenzoates; Rabbits; Serotonin; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Potassium-Chloride Symporters; Vasoconstriction