The renin-angiotensin system during pregnancy in chronically instrumented, conscious rats. 
Whether the renin-angiotensin system is activated during rat gestation is controversial.  Therefore we serially assessed plasma renin activity in unrestrained, chronically instrumented conscious rats during pregnancy and the postpartum period.  Plasma renin activity was 3.26 +/- 0.30, 2.80 +/- 0.31, and 2.70 +/- 0.26 ng.ml-1.hr-1 on gestational days 6, 12, and 20, respectively.  When the same rats were studied after delivery, plasma renin activity was 1.87 +/- 0.29, 1.81 +/- 0.09, and 2.31 +/- 0.35 ng.ml-1.hr-1 on postpartum days 3, 6, and 11, respectively.  Levels measured during pregnancy were significantly greater than in the postpartum period (p less than 0.05 or less than 0.01).  We then evaluated potential functional consequences of the renin-angiotensin system in gravid rats.  Near term, renal hemodynamics fall from the peak levels of midgestation; we tested whether angiotensin II mediates this apparent vasoconstriction.  Captopril (1.5 mg/kg, 1.5 mg.kg-1.hr-1) was acutely administered to lower circulating angiotensin II.  The drug produced an 80% inhibition of angiotensin I pressor response, a tenfold elevation in plasma renin activity, but caused the same degree of mild renal vasodilation in rats whether they were virgin or pregnant.  We also tested whether prior occupancy of receptors by endogenous hormone or receptor downregulation mediates the attenuated pressor response to angiotensin II observed during late pregnancy.  Acute administration of captopril failed to augment refractory pressor responsiveness.  Chronic treatment with enalaprilat (2.0 mg.kg-1.day-1 by osmotic minipump) also did not restore pressor responsiveness.  But, in our hands, chronic administration of enalaprilat most likely failed to lower plasma angiotensin II.  In summary, we suggest that during rat gestation (1) the renin-angiotensin system is activated, (2) angiotensin II does not mediate the apparent renal vasoconstriction observed near term, (3) prior receptor occupancy by endogenous hormone is not responsible for the attenuated pressor response to angiotensin II, and (4) long-term treatment with enalaprilat can produce hypotension without reducing plasma concentrations of angiotensin II.