Evidence that acetylcholine-mediated hyperpolarization of the rat small mesenteric artery does not involve the K+ channel opened by cromakalim.

1. Acetylcholine causes a concentration-dependent hyperpolarization of the rat small mesenteric artery (diameter at 100 mmHg, 200-400 microns). In the absence of tone the average potential change was from approximately -60 to -75 mV. In the presence of tone induced by endothelin-1 (20 nM), acetylcholine caused vasorelaxation in association with a marked hyperpolarization; from approximately -32 to -71 mV. 2. A number of compounds known to antagonize the actions of cromakalim were tested for their ability to block responses to acetylcholine. Glibenclamide (0.1-3 microM), phentolamine (10-100 microM) and alinidine (1-30 microM) caused a concentration-dependent depolarization of the rat small mesenteric artery which was not dependent on an intact endothelium. Glibenclamide was approximately 10 times more potent than either phentolamine or alinidine, a similar ratio to their potency as antagonists of cromakalim. 3. In the presence of concentrations of the cromakalim antagonists which functionally inhibited responses to cromakalim, only phentolamine and alinidine had a significant effect on the hyperpolarization and functional responses to acetylcholine. Glibenclamide was without effect at the concentrations used. 4. Experiments on pig coronary artery, where acetylcholine causes vasoconstrictor responses, showed that phentolamine and alinidine have some anti-muscarinic activity which could account for their ability to affect vasorelaxant/hyperpolarization responses to acetylcholine in the rat small mesenteric artery. 5. The results suggest that the acetylcholine-mediated hyperpolarization observed in the rat small mesenteric artery does not involve K+ channels opened by cromakalim. This finding differs from other studies performed on the rabbit middle cerebral artery which show hyperpolarizing responses to acetycholine to be glibenclamide-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)