INHIBITION OF THE ACETYLCHOLINE-INDUCED RELAXATION OF CANINE ISOLATED BASILAR ARTERY BY POTASSIUM-CONDUCTANCE BLOCKERS

Canine basilar artery rings precontracted with 5-hydroxytryptamine (0.1-0.5-mu-M) relaxed in the presence of acetylcholine (25-100-mu-M), sodium nitroprusside (0.1-mu-M), 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. Since 4-AP and similar agents are used to increase myogenic tone, the absence of the endothelium may be mistakenly assumed in the presence of these agents.