Hypertension in pregnancy is associated with elevated maternal and fetal mortality rates. Two major pathophysiological alterations which are known to occur in the pregnant hypertensive are elevated arterial blood pressure and chronic reduction in uterine blood flow. In previous studies from our laboratory we have investigated maternal and fetal effects of reduced uterine blood flow and have shown that decreased uterine perfusion can significantly alter fetal oxygenation. In the present proposal, we plan to utilize a renal hypertensive pregnant sheep model to evaluate hypertension induced alterations in uterine hemodynamic. In this study, the effects of renovascular hypertension on maternal and fetal cardiovascular, respiratory and biochemical parameters will be evaluated. Renal hypertension will be produced by unilateral nephrectomy and a 50% reduction in renal blood flow to the remaining kidney. Renal hypertension will be produced at 118 days gestation (term 145 days), eight days after maternal and fetal instrumentation (110 days gestation). Maternal arterial blood pressure changes will be measured from 90 days gestation to 142 days of gestation, at which time animals will be sacrificed for evaluation of fetal growth. During the period of instrumentation, maternal and fetal blood pressure, heart rate, blood gas values, oxygen content, pH, lactate, glucose and electrolytes will be determined. Because renal hypertension activates the renin angiotensin system, plasma renin activity and angiotensin II will also be measured. The ability of the altered renin-angiotensin system to modify prostaglandin levels will be investigated by measuring maternal arterial and uterine venous prostaglandin (PGD2, PGE2 and 6 keto PGF1Alpha) levels. In addition, uterine and femoral blood flow and their calculated vascular resistances will be determined. These measurements will allow us to determine if resistance changes occur in both vascular beds or if these changes are specific for the uterine vasculature. Finally throughout the experimental period (90-142 days gestation) systemic and local responses to vasoconstrictors (angiotensin II, norepinephrine and serotonin) will be evaluated to determine if renal hypertension alters vascular reactivity thus leading to increased vascular resistance. These studies will greatly improve our understanding of the effects of renal hypertension on the mother and fetus.
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