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 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.
Dai
Yun
Y
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, USA.
Zhang
John
J
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D002034:Bumetanide / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006016:Glycolates / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008698:Mesylates / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D018118:Chloride Channels; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D019332:Endothelin-1; D006016:Glycolates; D008698:Mesylates; D009579:Nitrobenzoates; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; C045880:methanesulfonic acid; D012701:Serotonin; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D009544:Niflumic Acid; C015765:MK 473