Ge Z D, Zhang X H, Fung P C, He G W
Grantham Hospital, Department of Surgery, The University of Hong Kong, Aberdeen, Hong Kong SAR, China.
Cardiovasc Res. 2000 Jun;46(3):547-56. doi: 10.1016/s0008-6363(00)00040-7.
It is controversial whether endothelium-dependent relaxation resistance to inhibitors of nitric oxide (NO) and prostacyclin synthases is completely attributed to endothelium-derived hyperpolarizing factor (EDHF). This study examined NO release and K+ channels involved in endothelium-dependent relaxation and hyperpolarization resistance to N(G)-nitro-L-arginine (L-NNA) and indomethacin in coronary arteries with emphasis on the microarteries.
NO release, isometric force, and membrane potential of porcine coronary arteries were measured using a NO-specific electrode, wire myograph, and microelectrode, respectively.
In large arteries pretreated with indomethacin, bradykinin (BK) evoked a rise in [NO] from 5.5+/-2.4 nM to 105.0+/-19.6 nM and hyperpolarization. L-NNA treatment significantly reduced the BK-stimulated rise in [NO] to 32.1+/-11.3 nM but did not affect the hyperpolarization. In the presence of indomethacin and L-NNA, U46619 contracted and depolarized (from -51+/-3 mV to -30+/-4 mV) vascular smooth muscle in microarteries. The addition of BK produced dose-dependent relaxation (maximal: 70.2+/-5.7%) and repolarization (membrane potential: -50+/-4 mV). Oxyhemoglobin eliminated indomethacin and L-NNA-resistance rise in [NO] but not relaxation (42.3+/-4.4%) and repolarization (-40+/-2 mV) by BK. Tetraethylammonium, charybdotoxin, and iberiotoxin partially decreased the BK-induced responses. Apamin alone did not affect the relaxation by BK; however, in combination with charybdotoxin it almost completely abolished the BK-induced relaxation and hyperpolarization.
In porcine coronary arteries, both EDHF and NO contribute to BK-induced relaxation resistance to indomethacin and L-NNA. Large conductance Ca2+-activated K+ channels (BK(Ca)) may play an important role in mediating the BK-induced responses and small conductance Ca2+-activated K+ channels might function as 'backup' mechanisms when BK(Ca) is curtailed.
一氧化氮（NO）和前列环素合酶抑制剂对内皮依赖性舒张的抵抗是否完全归因于内皮衍生超极化因子（EDHF）仍存在争议。本研究检测了冠状动脉（重点是微动脉）中参与内皮依赖性舒张以及对N(G)-硝基-L-精氨酸（L-NNA）和吲哚美辛超极化抵抗的NO释放和钾通道。
分别使用NO特异性电极、线肌张力测定仪和微电极测量猪冠状动脉的NO释放、等长力和膜电位。
在预先用吲哚美辛处理的大动脉中，缓激肽（BK）使[NO]从5.5±2.4 nM升高至105.0±19.6 nM并引起超极化。L-NNA处理显著将BK刺激的[NO]升高降低至32.1±11.3 nM，但不影响超极化。在吲哚美辛和L-NNA存在的情况下，U46619使微动脉中的血管平滑肌收缩并去极化（从-51±3 mV至-30±4 mV）。加入BK产生剂量依赖性舒张（最大：70.2±5.7%）和复极化（膜电位：-50±4 mV）。氧合血红蛋白消除了吲哚美辛和L-NNA抵抗的[NO]升高，但不影响BK引起的舒张（42.3±4.4%）和复极化（-40±2 mV）。四乙铵、大电导钙激活钾通道阻断剂（charybdotoxin）和iberiotoxin部分降低了BK诱导的反应。单独使用蜂毒明肽不影响BK引起的舒张；然而，与大电导钙激活钾通道阻断剂联合使用时，它几乎完全消除了BK诱导的舒张和超极化。
在猪冠状动脉中，EDHF和NO均参与BK诱导的对吲哚美辛和L-NNA的舒张抵抗。大电导钙激活钾通道（BK(Ca)）可能在介导BK诱导的反应中起重要作用，当BK(Ca)受到抑制时，小电导钙激活钾通道可能作为“备用”机制发挥作用。
