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Kidney Week

Abstract: TH-PO739

Intrapartum Sildenafil Therapy Does Not Impair Renal Function in Young Adult Offspring of Preeclamptic Dahl S Rats

Session Information

Category: Women’s Health and Kidney Diseases

  • 2000 Women’s Health and Kidney Diseases

Authors

  • Turbeville, Hannah R., 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 increased susceptibility to hypertension and renal function loss. We have shown that sildenafil citrate, a phosphodiesterase-5 (PDE-5) inhibitor, improves the maternal syndrome of preeclampsia in the Dahl S rat and reduces blood pressure of their offspring up to 21 weeks of age; however, long term kidney function in these offspring has not been examined. We hypothesized that PDE-5 inhibition during preeclamptic pregnancy improves long-term BP without significant reduction in renal function.

Methods

Female Dahl S rats on a 0.3% salt diet 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 12 weeks of age. Urine was collected (n=18-27/group) for measurement of urinary protein (Bradford assay) and creatinine (Jaffe reaction). Plasma was also collected at euthanasia (n=13-17/group) for measurement of blood urea nitrogen (BUN, enzymatic method) and creatinine, and creatinine clearance was calculated.

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. No significant differences in proteinuria were observed (VEH male: 102±8; SLD male: 101±8; VEH female: 55±5; SLD female: 75±6 mg/day). No significant differences in BUN were found between either sex or treatment group (VEH: 20.3±0.8; SLD: 18.16±0.7 mg/dL).While expected sex differences in creatinine clearance were maintained, there was no significant difference between the treatment groups (VEH male: 0.75±0.05; SLD male: 0.70±0.05; VEH female: 0.56±0.07; SLD female: 0.64±0.06 mL/min/g renal mass).

Conclusion

These data support the hypothesis that the use of a PDE-5 inhibitor during preeclamptic pregnancy improves the long-term BP without reduction of renal function in the offspring at 12 weeks of age.

Funding

  • NIDDK Support