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 synthas e inhibitor N-omega-nitro-L-arginine. We have now studied the effects of K+-channel blockers on the hyperpolarization responses to ACh in re sting and norepinephrine-contracted rat mesenteric arteries. We also m easured tension simultaneously to determine whether the inhibitory eff ects of these agents on relaxation could be correlated to their effect s on hyperpolarization. Glibenclamide had no significant effect on the hyperpolarization or relaxation. Tetraethylammonium (TEA, 5 mM) inhib ited the hyperpolarization to ACh significantly to a similar extent in both the resting and norepinephrine-stimulated arteries. Charybdotoxi n (100-150 nM) caused only a small but significant inhibition. Apamin (0.3 mu M) was the most effective in inhibiting the hyperpolarization in resting arteries. It was less effective in the norepinephrine-contr acted arteries. A combination of apamin and charybdotoxin completely a bolished the hyperpolarization responses in both conditions. The relax ation to ACh was correlated to hyperpolarization. In all cases, the in hibition of the relaxation by the K+-channel blockers could be account ed for by their effects on the hyperpolarization. These results indica te that Ca2+-activated K+ channels, especially those sensitive to apam in, may be the major ion channels mediating endothelium-dependent hype rpolarization to ACh.