O2-dependent modulation of calf pulmonary artery tone by lactate: potential role of H2O2 and cGMP.
O2-dependent modulation of calf pulmonary artery tone by lactate: potential role of H2O2 and cGMP.
复制标题
乳酸对小牛肺动脉张力的 O2 依赖性调节：H2O2 和 cGMP 的潜在作用。
DOI：
10.1152/ajplung.1993.264.2.l141
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Wolin,MS
中科院分区：
文献类型：
--
作者：
Omar,HA;Mohazzab,KM;Mortelliti,MP;Wolin,MS
研究发现，乳酸可使经 20-30 mM K+ 预收缩的、已去除内皮的孤立小腿肺动脉松弛。对这种反应机制的检查表明，它似乎是 O2 依赖性的，并通过鸟苷 3',5'-环单磷酸 (cGMP) 介导，因为它会因缺氧（N2 气氛，PO2 = 8-10 Torr）而减少，并且因为用亚甲基蓝抑制可溶性鸟苷酸环化酶激活可以消除松弛，并且可以通过 cGMP 选择性磷酸二酯酶拮抗剂增强（M & B 22948）。乳酸松弛不是通过前列腺素形成或精氨酸衍生的一氧化氮介导的，因为吲哚美辛或硝基-L-精氨酸分别不会改变反应。仅在抑制铜锌超氧化物歧化酶（通过二乙基二硫代氨基甲酸酯预处理）后，乳酸才会显着增强光泽精引发的化学发光（一种潜在的超氧阴离子检测器）。丙酮酸 (5 mM) 仅产生最小的松弛并且不会显着增加化学发光。在动脉平滑肌的匀浆部分中，需要 NAD 加乳酸或 NADH 才能观察到化学发光增加。观察到乳酸会增加小腿肺动脉平滑肌缺氧时的收缩和缺氧后复氧时的舒张，这与氧气（而非氮气）气氛下音调产生的降低有关。因此，乳酸（而非丙酮酸）似乎通过 NADH 依赖性超氧阴离子的产生增加细胞内 H2O2 的产生，从而在小牛肺动脉中引起 cGMP 介导的松弛，并且这种松弛机制的激活可调节 O2 引发的音调反应。
Lactate was found to produce a relaxation of isolated endothelium-removed calf pulmonary arteries precontracted with 20–30 mM K+. Examination of the mechanism of this response indicates that it appears to be O2 dependent and mediated via guanosine 3',5'-cyclic monophosphate (cGMP), since it is reduced by hypoxia (N2 atmosphere, PO2 = 8-10 Torr) and because the relaxation was both eliminated by inhibition of soluble guanylate cyclase activation with methylene blue and enhanced by an antagonist of cGMP-selective phosphodiesterases (M & B 22948). Relaxation to lactate is not mediated via prostaglandin formation or arginine-derived nitric oxide, since indomethacin or nitro-L-arginine, respectively, did not alter the response. Lucigenin-elicited chemiluminescence, a potential detector of superoxide anion, was significantly increased by lactate only after inhibition of Cu-Zn-superoxide dismutase (via pretreatment with diethyldithiocarbamate). Pyruvate (5 mM) produced only minimal relaxation and did not significantly increase chemiluminescence. In the homogenate fraction of the arterial smooth muscle, NAD plus lactate or NADH was required to observe increased chemiluminescence. The calf pulmonary arterial smooth muscle contraction to hypoxia and relaxation to posthypoxic reoxygenation was observed to be increased by lactate, associated with a reduced level tone generation under O2 but not N2 atmosphere. Thus lactate, but not pyruvate, appears to cause a cGMP-mediated relaxation in the calf pulmonary artery through an increased intracellular H2O2 generation via the NADH-dependent production of superoxide anion, and activation of this relaxing mechanism modulates O2-elicited tone responses.