NITRIC-OXIDE HYPERPOLARIZES RABBIT MESENTERIC-ARTERIES VIA ATP-SENSITIVE POTASSIUM CHANNELS
NITRIC-OXIDE HYPERPOLARIZES RABBIT MESENTERIC-ARTERIES VIA ATP-SENSITIVE POTASSIUM CHANNELS
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DOI：
10.1113/jphysiol.1995.sp020789
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发表时间：
1995-07-01
影响因子：
5.5
通讯作者：
BRAYDEN, JE
中科院分区：
文献类型：
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作者：
MURPHY, ME;BRAYDEN, JE
1. 一氧化氮 (NO) 放松血管平滑肌 (VSM) 的机制尚不完全清楚。一种可能性是 NO 使膜超极化，从而减少 Ca2+ 通过电压依赖性 Ca2+ 通道的进入。本研究采用细胞内微电极记录NO对兔肠系膜动脉膜电位的影响。 2． NO，由 3-morpholinosydnonimine (SIN-1，3 mu M) 释放，使动脉从 -53.1 +/- 5.7 mV 的静息膜电位可逆性超极化 -9.5 +/- 4.0 mV（意味着 +/- S.D.，n = 97）。超极化被氧合血红蛋白(20μM)阻断，并且仅发生在用N-omega-硝基-L-精氨酸(100μM)预处理或剥去内皮的动脉中。3． SIN-1的作用是浓度依赖性的(EC(50)大约为0.4μM)，并且它的剂量反应被扎普司特(100μM)(一种cGMP特异性磷酸二酯酶抑制剂)左移。4． SIN-1 引起的超极化会因细胞外 K+ 浓度的变化而改变，但不会因 Ca2+、Na+ 或 Cl- 的变化而改变。超极化被格列本脲阻断（IC50大约为0.15μM），但不能被apamin（3-300nM）、钡（5-150μM）、四乙铵（0.1-10mM）或4-氨基吡啶（5-500μM）阻断。由 lemakalim (0.03-3 μM)（一种 ATP 敏感钾通道 (K-ATP) 激活剂）引起的超极化对这些 K+ 通道阻断剂表现出相同的敏感性，而添加乙酰胆碱 (3 μM) 引发的内皮源性超极化因子引起超极化 (-15.3 +/- 6.2 mV)，该超极化被 apamin 阻断，但不被任何其他药物阻断。代理.5。这些结果表明，NO 通过激活 K-ATP 通道使兔肠系膜动脉中的 VSM 超极化，其中 cGMP 的积累作为中间步骤。
1. Nitric oxide (NO) relaxes vascular smooth muscle (VSM) by mechanisms which are not fully understood. One possibility is that NO hyperpolarizes membranes, thereby diminishing Ca2+ entry through voltage-dependent Ca2+ channels. In the current study, the effects of NO on membrane potential of rabbit mesenteric arteries were recorded using intracellular microelectrodes.2. NO, released by 3-morpholinosydnonimine (SIN-1, 3 mu M), reversibly hyperpolarized arteries by -9.5 +/- 4.0 mV (means +/- S.D., n = 97) from a resting membrane potential of -53.1 +/- 5.7 mV. The hyperpolarization was blocked by oxyhaemoglobin (20 mu M), and only occurred in arteries pre-treated with N-omega-nitro-L-arginine (100 mu M) or denuded of endothelium.3. The effect of SIN-1 was concentration dependent (EC(50) approximate to 0.4 mu M), and its dose response was shifted to the left by zaprinast (100 mu M), an inhibitor of cGMP-specific phosphodiesterases.4. The hyperpolarization due to SIN-1 was modified by changes in extracellular K+ concentration, but not by changes in Ca2+, Na+ or Cl-. The hyperpolarization was blocked by glibenclamide (IC50 approximate to 0.15 mu M), but not by apamin (3-300 nM), barium (5-150 mu M), tetraethylammonium (0.1-10 mM), or 4-aminopyridine (5-500 mu M). The hyperpolarization due to lemakalim (0.03-3 mu M), an activator of ATP-sensitive potassium channels (K-ATP), displayed the same sensitivities to these K+ channel blocking agents, whereas the endothelium-derived hyperpolarizing factor, triggered by the addition of acetylcholine (3 mu M), caused a hyperpolarization (-15.3 +/- 6.2 mV) that was blocked by apamin, but not by any other agent.5. These results suggest that NO hyperpolarizes VSM in rabbit mesenteric arteries by activating K-ATP channels, with the accumulation of cGMP as an intermediate step.