Chen G, Cheung D W
University of Ottawa Heart Institute, Ontario, Canada.
Am J Physiol. 1997 May;272(5 Pt 2):H2306-12. doi: 10.1152/ajpheart.1997.272.5.H2306.
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.
在一氧化氮合酶抑制剂Nω-硝基-L-精氨酸存在的情况下，乙酰胆碱（ACh）可诱导大鼠肠系膜动脉出现内皮依赖性超极化。我们现在研究了钾通道阻滞剂对静息和去甲肾上腺素收缩的大鼠肠系膜动脉中ACh超极化反应的影响。我们还同时测量了张力，以确定这些药物对舒张的抑制作用是否与其对超极化的影响相关。格列本脲对超极化或舒张无显著影响。四乙铵（TEA，5 mM）在静息和去甲肾上腺素刺激的动脉中均显著抑制ACh引起的超极化，抑制程度相似。大蝎毒素（100 - 150 nM）仅引起轻微但显著的抑制。蜂毒明肽（0.3 μM）在抑制静息动脉超极化方面最为有效。在去甲肾上腺素收缩的动脉中效果较差。蜂毒明肽和大蝎毒素联合使用在两种情况下完全消除了超极化反应。ACh引起的舒张与超极化相关。在所有情况下，钾通道阻滞剂对舒张的抑制作用可由其对超极化的影响来解释。这些结果表明，钙激活钾通道，尤其是对蜂毒明肽敏感的那些通道，可能是介导内皮依赖性ACh超极化的主要离子通道。
