Biochemical and Molecular Biological Investigation of the Pregnancy Associated Uterine Blood Flow Increase-As a Basic Study for Developing Future Treatment of Intrauterine Growth Retardation-

妊娠使子宫动脉血流量增加约30倍，为发育中的胎儿提供氧气和营养，其生理机制尚未完全阐明。最近，脉冲多普勒超声研究表明，这种生理增加的子宫血流的可能性，在某些情况下，胎儿宫内发育迟缓（IUGR）受到干扰。因此，本研究的目的是探讨两个主要的鸟苷酸环化酶系统，一氧化氮（NO）/可溶性鸟苷酸系统（sGC）和C型利钠肽（CNP）/颗粒鸟苷酸环化酶-B（GC-B）系统，在妊娠期间子宫动脉血流的调节中，我们发现妊娠增加了内皮型NO合酶的蛋白和mRNA表达，妊娠绵羊子宫动脉中eNOS、sGC、CNP和GC-B含量增加，而肾动脉和网膜动脉中eNOS、sGC、CNP和GC-B含量无明显变化。通过cGMP pro估计的sGC和GC-B的体外酶活性 ...更多信息 妊娠绵羊子宫动脉组织中D_1、D_2、D_3、D_4、D_5、D_6、D_7、D_8、D_9、D_10、D_9在非妊娠绵羊中未观察到子宫动脉中cGMP生成的局部上调。因此，NO/sGC和CNP/GC-B通路在妊娠期绵羊子宫动脉中特异性上调，通过增加局部cGMP的生成而促进子宫动脉血流量增加。这表明了一种可能性，鸟苷酸环化系统的调节可能也参与了妊娠期子宫动脉血流量的增加。轻度子痫前期孕妇血浆cGMP浓度显著高于重度子痫前期孕妇，且伴有重度高血压及IUGR，提示重度子痫前期孕妇全身和/或局部鸟苷酸环化酶系统的上调可能恶化。少

Pregnancy increases uterine artery blood flow approximately 30 fold for supply oxygen and nutrition to developing fetus, the physiological mechanism of which has not been fully clarified. Recently, pulsed Doppler ultrasound investigations suggested a possibility that this physiological increase of uterine blood flow was disturbed in some cases of intrauterine growth retardation (IUGR). Therefore, the aim of the study is to investigate, the possible involvement of two major guanylate cyclase systems, nitric oxide (NO) / soluble gaunylate system (sGC) andC-type natriuretic peptide (CNP) / particulate guanylate cyclase-B (GC-B) system, in the regulation of uterine artery blood flow during pregnancy.In this study we revealed that pregnancy increased the protein and mRNA expression of endothelial NO synthase (eNOS), sGC, CNP and GC-B increased in uterine artery, but not renal nor omental arteries from pregnant sheep. The in vitro enzyme activities of both sGC and GC-B, estimated by cGMP pro … More duction, in the tissues of uterine arteries from pregnant sheep was significantly higher than those renal or omental arteries. This local up-regulation of cGMP generation in uterine artery was not observed in nonpregnant sheep. Thus, both NO/sGC and CNP/GC-B pathways were specifically up-regulated in ovine uterine artery during pregnancy, contributing to uterine artery blood flow increase by augmenting local cGMP generation.Moreover, the plasma cGMP concentrations in normal pregnant women were significantly elevated during pregnancy, which suggested a possibility that the up-regulation of guanylate cyclate system might be also involved in human uterine artery blood flow increase during pregnancy. The plasma cGMP concentrations in mild preeclampsia pregnant women were significantly higher than those in severe preeclampsia, for all maternal severe hyper tension as well as complication with IUGR.These data all together suggested an interesting possibility that the preganacy associated up-regulation of systemic and/or local guanylate cyclase system might be deteriorated in cases of maternal severe preeclampsia. Less