Comparison of rabbit coronary arterial relaxation induced by acetylcholine and lemakalim: activation of ATP sensitive potassium channels.
OBJECTIVE
The purpose was to assess the role of ATP sensitive potassium channels (KATP) in endothelium dependent vasodilatation induced by acetylcholine, or endothelium independent vasodilatation induced by lemakalim in rabbit coronary arteries.


METHODS
The effect of glibenclamide, a specific inhibitor of KATP, 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.


METHODS
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.


RESULTS
K+ (30 mmol.litre-1) and PGF2 alpha (3 mumols.litre-1) caused comparable contraction (p greater than 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 mumol.litre-1) were reduced from 82(SEM 2.7)% and 93(2.8)% to 71(2.4)% and 82(2.7)% (p less than 0.05), and to 63(3.2)% and 79(4.5)% (p less than 0.05 or less than 0.01) by glibenclamide (3 and 10 mumols.litre-1) respectively in PGF2 alpha precontracted rings; and also attenuated (p less than 0.05 or less than 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 less than 0.01).


CONCLUSIONS
These results suggest that activation of KATP 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 KATP.
Jiang
C W
CW
Department of Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom.
Poole-Wilson
P A
PA
Collins
P
P
D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D019806:Cromakalim; D015237:Dinoprost / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000255:Adenosine Triphosphate; D015237:Dinoprost; D000109:Acetylcholine; D005905:Glyburide