Omar H A, Figueroa R, Tejani N, Wolin M S
Department of Physiology, New York Medical College, Valhalla 10595.
Am J Obstet Gynecol. 1993 Oct;169(4):912-8. doi: 10.1016/0002-9378(93)90026-f.
Our purpose was to determine the vasoactive effects and mechanism of action of lactate in human placental vessels by means of isometric muscle bath studies.
Isolated 1 to 2 mm human placental arteries and veins from normal term pregnancies, precontracted with prostaglandin F2 alpha and incubated under a PO2 of approximately 35 torr were exposed to lactate, 1 to 10 mmol/L, (pH 7.4), pyruvate, hydrogen peroxide, nitroglycerin, or forskolin. The effects of endothelium removal or inhibitors of cyclooxygenase (indomethacin 10 mumol/L) and L-arginine metabolism (nitro-L-arginine 30 mumol/L) on the response to lactate and the effects of an antagonist of guanylate cyclase activation (methylene blue 10 mumol/L), cyanide (1 mmol/L), and hypoxia (PO2 8-10 torr) on responses to all agents were determined by analysis of variance and t test statistics.
Lactate-elicited dose-dependent relaxation was not inhibited by endothelium removal, indomethacin, or nitro-L-arginine but was attenuated by methylene blue, cyanide, and hypoxia. Relaxation to hydrogen peroxide was inhibited by methylene blue and cyanide but not hypoxia. Relaxation to nitroglycerin was inhibited only by methylene blue, and relaxation to forskolin was not inhibited by these probes. Pyruvate did not produce a significant relaxation.
These findings suggest that lactate causes relaxation in the human placental vessels by an oxygen and cyclic guanosine-3':5'-monophosphate-dependent mechanism, which may involve the generation of hydrogen peroxide but not the metabolism of arginine. Lactate-induced dilatation may be of importance during labor and in situations of acute and chronic fetal hypoxia.
我们的目的是通过等长肌槽实验研究来确定乳酸在人胎盘血管中的血管活性作用及作用机制。
从足月正常妊娠中分离出1至2毫米的人胎盘动脉和静脉，用前列腺素F2α预收缩，并在约35托的氧分压下孵育，然后暴露于1至10毫摩尔/升的乳酸（pH 7.4）、丙酮酸、过氧化氢、硝酸甘油或福斯高林。通过方差分析和t检验统计来确定去除内皮或环氧化酶抑制剂（吲哚美辛10微摩尔/升）和L-精氨酸代谢抑制剂（硝基-L-精氨酸30微摩尔/升）对乳酸反应的影响，以及鸟苷酸环化酶激活拮抗剂（亚甲蓝10微摩尔/升）、氰化物（1毫摩尔/升）和低氧（氧分压8 - 10托）对所有药物反应的影响。
乳酸引起的剂量依赖性舒张不受去除内皮、吲哚美辛或硝基-L-精氨酸的抑制，但被亚甲蓝、氰化物和低氧减弱。对过氧化氢的舒张被亚甲蓝和氰化物抑制，但不受低氧抑制。对硝酸甘油的舒张仅被亚甲蓝抑制，对福斯高林的舒张不受这些探针抑制。丙酮酸未产生明显舒张。
这些发现表明，乳酸通过氧和环磷酸鸟苷依赖性机制使人胎盘血管舒张，这可能涉及过氧化氢的生成但不涉及精氨酸的代谢。乳酸诱导的扩张在分娩期间以及急性和慢性胎儿缺氧情况下可能具有重要意义。
