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Abstract: FR-PO314

Intrapartum PDE-5 Inhibition Lowers Blood Pressure and Renal Injury in Young Adult Offspring of Preeclamptic Dahl S Rats

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Turbeville, Hannah R., University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Didion, Sean, University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Garrett, Michael R., University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Sasser, Jennifer M., University of Mississippi Medical Center, Jackson, Mississippi, United States
Background

Up to 10% of pregnancies are complicated by preeclampsia, and up to 15 million Americans are offspring of preeclamptic pregnancies. The Developmental Origins of Health and Disease hypothesis proposes that an adverse intrauterine environment programs the fetus to develop high blood pressure (BP) from early childhood, and evidence shows that offspring of preeclamptic pregnancies have increased risk of hypertension and CKD. Animal models of hypertension in pregnancy have shown that sildenafil citrate, a phosphodiesterase-5 (PDE-5) inhibitor that prolongs NO-cGMP signaling, improves the maternal syndrome of preeclampsia; however, the effects of perinatal use on long term fetal outcomes have not been reported. Here, we test the hypothesis that PDE-5 inhibition during preeclamptic pregnancy improves long-term BP and renal injury in the offspring.

Methods

Female Dahl S rats (n=16) on a 0.3% salt diet, a previously characterized model of preeclampsia, were mated and treated orally with sildenafil (50 mg/kg/day) or vehicle from gestational day 10 to delivery. Lactating dams and offspring were on normal chow for the duration of the study, and measurements were made at 11 weeks of age.

Results

Systolic BP (n=5-9/group, tail cuff) was greater in Dahl S rats of untreated mothers compared to offspring of sildenafil treated dams (VEH: 177±4 mmHg; SLD: 158±2 mmHg; p=0.0001). BP data were pooled due to lack of significant sex differences between treated groups. Tubulointerstitial fibrosis (n=3/group) was measured in kidney sections stained with Masson’s trichrome. Tubulointerstitial fibrosis is increased in male Dahl S offspring of untreated mothers as compared with offspring of sildenafil treated dams (Area: VEH: 9.0 ±0.6%; SLD: 5.0 ±0.6%, p=0.006), but no differences were observed in female rats (VEH: 5.3 ±0.7%; SLD: 6.0 ±0.6%). Urine was collected for measurement of urinary protein (Bradford assay), but no significant differences in proteinuria were observed (VEH male: 87 ±23 mg/day; SLD male: 138 ±18 mg/day; VEH female: 64 ±9 mg/day; SLD female: 53 ±7mg/day).

Conclusion

These data support the hypothesis that use of a PDE-5 inhibitor during preeclamptic pregnancy improves the long-term BP and renal injury in the offspring.

Funding

  • NIDDK Support