Sildenafil Citrate Does Not Reprogram Risk of Hypertension and Chronic Kidney Disease in Offspring of Preeclamptic Pregnancies in the Dahl SS/Jr Rat

Abstract

Background Preeclampsia is a disorder of pregnancy with accompanying high disease and economic burdens in the United States. Evidence supporting longstanding effects of preeclampsia on the offspring of affected pregnancies is high, but the effects of current antihypertensive therapies for preeclampsia on cardio-renal outcomes are largely unknown. The purpose of this study was to test the hypothesis that sildenafil citrate, a phosphodiesterase-5 inhibitor, reprograms the risk of hypertension and kidney disease in offspring of preeclamptic pregnancies by altering responses to secondary stressors. Methods Dahl SS/Jr rats on a 0.3% NaCl diet were mated. At gestational day 10, pregnant dams were randomized to vehicle diet or diet with sildenafil (50 mg/kg per day), which was continued until birth. Pups were weaned at 4 weeks of age and allowed to age on a 0.3% NaCl diet until 3 months of age. At this point, pups were randomized into three groups: baseline or no intervention, 2% NaCl diet challenge for 4 weeks, or a subpressor infusion of angiotensin II (200 ng/kg per minute) for 2 weeks. Results There were no differences among maternal treatment groups at baseline. Upon introduction of 2% NaCl diet, male offspring of sildenafil-Treated dams exhibited an attenuated rise in BP; however, this protection was not observed during angiotensin II infusion. Conclusions Our findings indicate that intrapartum sildenafil does not reprogram the risk of hypertension and kidney disease in offspring of preeclamptic pregnancies.