We propose to test the following hypothesis: 1) local release of endothelium derived nitric oxide (EDNO) plays a significant role in the increase in myometrial and endometrial blood flow observed during pregnancy.
The Specific Aim to test this part of the hypothesis would be to demonstrate the effects of selected inhibitors of EDNO synthesis in selectively decreasing uterine blood flow in pregnant rats at various stages of gestation using the hydrogen clearance technique. 2) This increase in gestation related release and action of EDNO in individual arterioles is more prominent for the uterine vascular bed (as compared to another visceral vascular bed).
The Specific Aim to test this part of the hypothesis would be, to demonstrate the developmental changes during gestation in basal and stimulated release and action of EDNO as well as the cyclic GMP mediated vasodilatory system of mesometrial arterioles of pregnant rats in vivo when compared to gastric submucosa arterioles using the in vivo microscopy technique; 3) The increase in ENDO release and action in the uterine vascular bed during pregnancy is modulated by sex steroids.
The Specific Aim to test this part of the hypothesis would be to demonstrate the modulating role of estradiol (E2) and progesterone (P) on the release and action of EDNO from the uterine vascular bed and the cellular mechanism of such action. Long Term Objectives The generation and actions of EDNO in increasing uterine blood flow (UBF) and diminishing uterine vascular resistance will have important basic and clinical implications. The results of these studies may indicate the regulatory raechanism by which EDNO release and action is increased during pregnancy and how sex steroids modulate this effect. The results would lay the foundation for future studies to assess the role of EDNO in the pathophysiology of certain diseased states associated with pregnancy, such as hypertension and diabetes, conditions where the fetus may be adversely affected.
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