Effect of K(+)-channel blockers on ACh-induced hyperpolarization and relaxation in mesenteric arteries.
Acetylcholine (ACh) induces endothelium-dependent hyperpolarization in the rat mesenteric artery in the presence of the nitric oxide synthase inhibitor N omega-nitro-L-arginine. We have now studied the effects of K(+)-channel blockers on the hyperpolarization responses to ACh in resting and norepinephrine-contracted rat mesenteric arteries. We also measured tension simultaneously to determine whether the inhibitory effects of these agents on relaxation could be correlated to their effects on hyperpolarization. Glibenclamide had no significant effect on the hyperpolarization or relaxation. Tetraethylammonium (TEA, 5 mM) inhibited the hyperpolarization to ACh significantly to a similar extent in both the resting and norepinephrine-stimulated arteries. Charybdotoxin (100-150 nM) caused only a small but significant inhibition. Apamin (0.3 microM) was the most effective in inhibiting the hyperpolarization in resting arteries. It was less effective in the norepinephrine-contracted arteries. A combination of apamin and charybdotoxin completely abolished the hyperpolarization responses in both conditions. The relaxation to ACh was correlated to hyperpolarization. In all cases, the inhibition of the relaxation by the K(+)-channel blockers could be accounted for by their effects on the hyperpolarization. These results indicate that Ca(2+)-activated K(+)-channels, especially those sensitive to apamin, may be the major ion channels mediating endothelium-dependent hyperpolarization to ACh.
Chen
G
G
University of Ottawa Heart Institute, Ontario, Canada.
Cheung
D W
DW
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001030:Apamin / Q000008:administration & dosage; D002118:Calcium / Q000502:physiology; D018999:Charybdotoxin / Q000008:administration & dosage; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology*; D005905:Glyburide / Q000008:administration & dosage; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000008:administration & dosage
D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D001030:Apamin; D019789:Tetraethylammonium; D000109:Acetylcholine; D005905:Glyburide; D002118:Calcium; D009638:Norepinephrine