Suzuki Yoshikatsu, Hattori Tomonori, Kajikuri Junko, Yamamoto Tamao, Suzumori Kaoru, Itoh Takeo
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Nagoya City University, Mizuho-ku, Nagoya 467-8601, Japan.
J Physiol. 2002 Nov 15;545(1):269-77. doi: 10.1113/jphysiol.2002.022384.
It remains unclear in pre-eclampsia whether or not a functional change occurs in the role played by prostacyclin in endothelium-dependent relaxation in resistance arteries. We examined this using human omental resistance arteries (obtained from pre-eclamptic or normotensive pregnant women) in the presence of N(G)-nitro-L-arginine (L-NNA, an inhibitor of nitric oxide synthase). In endothelium-intact strips from both groups, 9,11-epithio-11,12-methano-thromboxane A(2) (STA(2), a thromboxane A(2) mimetic) produced a contraction. Diclofenac (an inhibitor of cyclooxygenase) enhanced the STA(2) contraction only in the normotensive pregnant group (1.4 times control, P < 0.01). In the presence of STA(2), bradykinin (0.1 microM) produced an endothelium-dependent relaxation in both groups, the relaxation being significantly smaller for the pre-eclamptic group (P < 0.002). Diclofenac significantly attenuated the bradykinin-induced relaxation only for the normotensive pregnant group (31 % inhibition, P < 0.001). The bradykinin-induced membrane hyperpolarization consisted of diclofenac-sensitive and -insensitive components. The former, but not the latter, was significantly smaller in pre-eclampsia (-4.3 vs. -2.6 mV, P < 0.05). The concentrations of 6-keto-PGF(1alpha) (a stable metabolite of prostacyclin) in these arteries were significantly lower in pre-eclampsia in both the absence and presence of bradykinin (about 0.2-0.4 times the normotensive pregnant value in each case, P < 0.01). By contrast, both the relaxation and the membrane hyperpolarization in response to beraprost (10 nM, a stable analogue of prostacyclin) were similar between the two groups. We conclude that, in pre-eclampsia, a reduced part is played by prostaglandins in the endothelium-dependent relaxation seen in resistance arteries and that this may be due to a reduced production of prostacyclin by the endothelium.
在先兆子痫中，前列环素在阻力动脉内皮依赖性舒张中所起的作用是否发生功能变化仍不清楚。我们在存在N(G)-硝基-L-精氨酸（L-NNA，一种一氧化氮合酶抑制剂）的情况下，使用人网膜阻力动脉（取自先兆子痫或血压正常的孕妇）对此进行了研究。在两组内皮完整的血管条中，9,11-环氧-11,12-甲撑血栓素A(2)（STA(2)，一种血栓素A(2)类似物）引起收缩。双氯芬酸（一种环氧化酶抑制剂）仅在血压正常的孕妇组增强了STA(2)收缩（为对照的1.4倍，P < 0.01）。在存在STA(2)的情况下，缓激肽（0.1微摩尔）在两组中均引起内皮依赖性舒张，先兆子痫组的舒张明显较小（P < 0.002）。双氯芬酸仅在血压正常的孕妇组显著减弱了缓激肽诱导的舒张（抑制31%，P < 0.001）。缓激肽诱导的膜超极化由双氯芬酸敏感和不敏感成分组成。前者而非后者在先兆子痫中明显较小（-4.3对-2.6毫伏，P < 0.05）。在不存在和存在缓激肽的情况下，这些动脉中6-酮-PGF(1α)（前列环素的一种稳定代谢产物）的浓度在先兆子痫中均显著降低（每种情况下约为血压正常孕妇值的0.2 - 0.4倍，P < 0.01）。相比之下，两组对贝拉前列素（10纳摩尔，一种前列环素的稳定类似物）的舒张和膜超极化相似。我们得出结论，在先兆子痫中，前列腺素在阻力动脉内皮依赖性舒张中所起的作用减小，这可能是由于内皮前列环素生成减少所致。
