title: Inhibition of the acetylcholine-induced relaxation of canine isolated basilar artery by potassium-conductance blockers.
abstract: Canine basilar artery rings precontracted with 5-hydroxytryptamine (0.1-0.5 microM) relaxed in the presence of acetylcholine (25-100 microM), sodium nitroprusside (0.1 microM), or stimulation of the electrogenic sodium pump by restoration of extracellular K+ (4.5 mM) after K(+)-deprivation. Acetylcholine-induced relaxation is believed to be caused by the release of endothelium-derived relaxing factor (EDRF) and is prevented by mechanical removal of the endothelium, while relaxations induced by sodium nitroprusside or restarting of the sodium pump are endothelium-independent. Acetylcholine-induced relaxation was selectively blocked by pretreatment of the tissue with the nonselective K+ conductance inhibitors, 4-aminopyridine (4-AP, 3 mM), Ba2+ (1 mM), and tetraethylammonium (20 mM), 4-AP also blocked ACh-mediated relaxation in muscles contracted with elevated external K+. Relaxation of 5-hydroxytryptamine-induced contraction by sodium nitroprusside, or by addition of K+ to K(+)-deprived muscle, was not affected by 4-AP. Relaxation of basilar artery with acidified sodium nitrite solution (containing nitric oxide) was reduced by 4-AP. These results suggest that 4-AP and possibly Ba2+ inhibit acetylcholine-induced endothelium-dependent relaxation by inhibition of the action of EDRF on the smooth muscle rather than through inhibition of release of EDRF. The increase in K+ conductance involved in acetylcholine-induced relaxation is not due to ATP-inhibited K+ channels, as it is not blocked by glyburide (10(-6) M). Endothelium-derived relaxant factor(s) may relax smooth muscle by mode(s) of action different from that of sodium nitroprusside or by hyperpolarization due to the electrogenic sodium pumping.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: D A
authors.initials: DA
authors.lastname: Elliott
authors.forename: M
authors.initials: M
authors.lastname: Gu
authors.forename: B Y
authors.initials: BY
authors.lastname: Ong
authors.forename: D
authors.initials: D
authors.lastname: Bose
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D009599:Nitroprusside; D001464:Barium; D009569:Nitric Oxide; D011189:Potassium Chloride; D012964:Sodium; D015761:4-Aminopyridine; D000109:Acetylcholine; D005905:Glyburide