COMPARISON OF RABBIT CORONARY ARTERIAL RELAXATION INDUCED BY ACETYLCHOLINE AND LEMAKALIM - ACTIVATION OF ATP SENSITIVE POTASSIUM CHANNELS

Study objective - The purpose was to assess the role of ATP sensitive potassium channels (K(ATP)) in endothelium dependent vasodilatation induced by acetylcholine, or endothelium independent vasodilatation induced by lemakalim in rabbit coronary arteries. Design - The effect of glibenclamide, a specific inhibitor of K(ATP), on coronary artery relaxation induced by acetylcholine or lemakalim was investigated. The relaxing effectiveness of acetylcholine and lemakalim on coronary arteries precontracted with KCl (K+) or prostaglandin F2-alpha (PGF2-alpha) was compared. Experimental materials - Left epicardial coronary arteries from male New Zealand white rabbits (2.5-3.0 kg), killed by an overdose of pentobarbitone, were dissected free of connective tissue. Rings suspended in organ baths for the measurement of isometric tension. Measurements and main results - K+ (30 mmol-litre-1) and PGF2-alpha. (3-mu-mol.litre-1) caused comparable contraction (p > 0.05) in endothelium intact or endothelium denuded coronary arterial rings. Acetylcholine induced relaxation was greater in endothelium intact rings precontracted with PGF2-alpha than with K+ and was abolished by the removal of endothelium. Relaxations induced by acetylcholine (0.1 and 0.3-mu-mol.litre-1) were reduced from 82(SEM 2.7)% and 93(2.8)% to 71(2.4)% and 82(2.7)% (p < 0.05), and to 63(3.2)% and 79(4.50% (p < 0.05 or < 0.01) by glibenclamide (3 and 10 mu-mol.litre-1) respectively in PGF2-alpha precontracted rings; and also attenuated (p < 0.05 or < 0.01) in K+ precontracted rings. Lemakalim induced relaxation was greater in endothelium denuded rings precontracted with PGF2-alpha than with K+, and was markedly reduced by glibenclamide (p < 0.01). Conclusions - These results suggest that activation of K(ATP) may partially be involved in endothelium dependent relaxation induced by acetylcholine in rabbit coronary arteries. Lemakalim-induced endothelium independent relaxation results mainly from activation of K(ATP).