The factors that mediate the 30 to 50 percent increment in renal blood flow (RBF) and glomerular filtration rate (GFR) that occur in pregnancy are unknown. The research will examine the hypothesis that renal and extrarenal vascular synthesis of vasodilator prostaglandins, as well as modulation of tissue responsiveness to AII, may underlie the rise in RBF and decrease in renal and extrarenal vascular resistances seen in pregnancy. The studies will utilize rabbits during early and late gestation. Rabbits experience increments in GFR, blood levels of vasodilator prostaglandins and AII, as well as enhanced urinary PGE2 excretion during gestation similar to that observed in pregnant women.
The specific aims are: 1) To determine the dependence of RBF, systemic hemodynamics, and prostanoid synthesis on the renin-AII system during gestation. 2) To determine the dependence of RBF and systemic hemodynamics on prostanoid synthesis. 3) To determine whether there is a gestational change in the capacity of renal and extrarenal tissues to synthesize prostanoids in the absence and in the presence of AII. 4) To determine if there is a gestational change in the in-vitro mesenteric artery contractile response to AII that can be correlated with an observed gestational decrease in AII receptors. 5) To identify and characterize AII receptors in renal microvessels and determine whether there is a gestational effect on these receptors. 6) To evaluate the effect of estradiol in ovariectomized rabbits on AII receptors, tissue responses to AII, and prostanoid synthesis. The in-vivo studies will be done utilizing conscious, chronically instrumented rabbits. RBF will be determined via an implanted electromagnetic flow probe, cardiac output will be quantitated by the thermodilution technique, while blood pressure will be measured directly with a pressure transducer connected to an intra-arterial catheter. Prostanoids will be quantitated by radioimmunoassay. Renal vessels will be obtained by microdissection and AII binding will employ a radio-receptor assay. A deterioration in renal and systemic hemodynamics often heralds the onset of pre-eclampsia with attendant risks of fetal and maternal morbidity. It is anticipated that these studies will ultimately help define the pathophysiology of pregnancy induced hypertension.
