Abstract: SA-PO1072

Preeclamptic Pregnancy Exacerbates Renal Injury in Dahl Salt Sensitive (S) Rats

Session Information

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Rice, Hannah, 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

Preeclampsia results in increased susceptibility to stroke, heart attack, hypertension, and chronic kidney disease postpartum. Despite increased cardiorenal disease risk, recommendations for prevention in these patients have not been established due to a lack of evidence for the mechanisms responsible for disease progression or evaluation of optimal therapeutic regimens. The purpose of this study was to test the hypothesis that preeclampsia accelerates the progression of chronic kidney disease and is associated with changes in the nitric oxide (NO):endothelin-1 (ET-1) balance.

Methods

Dahl S rats on a 0.3% salt diet (previously characterized model of superimposed preeclampsia) who experienced 2 pregnancies (12 and 17 weeks of age) and virgin littermate controls were aged to 6 months. Rats were implanted with telemetry transmitters (DSI), mean arterial pressure (MAP) was recorded, and rats were placed in metabolic cages for 24 hour urine collection prior to tissue harvest.

Results

Prior pregnancy did not result in a further increase in MAP at 6 months in the already hypertensive Dahl S females (virgin:185±6.9 mm Hg, prior pregnancy:184.6±6.6 mm Hg, n=8-10). Despite similar BP, rats who experienced prior preeclamptic pregnancy had greater renal injury compared to virgin littermates. Urinary excretion of protein (96±20 vs 195±45 mg/day), nephrin (0.6±0.4 vs 3.1±1.2 µg/day), and podocalyxin (4.9±1.0 vs 21.0±7.6 µg/day) was higher compared to littermate controls (p<0.05, Bradford assay, Exocell ELISA). These measures of renal injury were corroborated by histological examination as kidneys from rats that experienced preeclampsia demonstrated greater glomerular sclerosis (2.9±0.3) compared to virgin littermates (2.5±0.3, p=0.05). Analysis of urine from Dahl S rats following 2 consecutive pregnancies indicated decreased NO bioavailability (13.0±5.0 vs 5.2±1.6 µmol/day, Cayman Chemical NOx Assay) and increased renal production of ET-1 (4.6±1.5 vs 11.9±3.5 pg/day, with no change in plasma levels of ET-1, R&D Systems Quantiglo ELISA) suggesting that there may be an imbalance in the NO and ET-1 systems following preeclamptic pregnancy.

Conclusion

These data support the hypothesis that alterations in the NO/ET-1 balance in the kidney could link the maternal syndrome of preeclampsia to the increased postpartum risk of cardiovascular and renal disease.

Funding

  • NIDDK Support