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-

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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