Superimposed Preeclampsia Exacerbates Postpartum Renal Injury Despite Lack of Long-Term Blood Pressure Difference in the Dahl Salt-Sensitive Rat

Abstract

Preeclampsia results in increased susceptibility to hypertension and chronic kidney disease postpartum; however, the mechanisms responsible for disease progression in these women remain unknown. The purpose of this study was to test the hypothesis that 2 mechanisms contribute to the link between the maternal syndrome of preeclampsia and the increased postpartum risk of cardiovascular and renal disease: (1) increased T cells in the kidney and (2) a decreased NO:ET-1 (endothelin-1) ratio. Dahl S rats (a previously characterized model of preeclampsia superimposed on chronic hypertension) who experienced 2 pregnancies and virgin littermate controls were studied at 6 months of age. Mean arterial pressure was measured via telemetry, and renal injury was assessed through both histological analysis and measurement of urinary markers including nephrin, podocalyxin, and KIM-1 (kidney injury marker 1). Contributing mechanisms were assessed through flow cytometric analysis of renal T cells, quantification of plasma TNF-α (tumor necrosis factor-α) and IL-10 (interleukin-10), and quantification of urinary concentrations of NO metabolites and ET-1. Although prior pregnancy did not exacerbate the hypertension at 6 months, this group showed greater renal injury compared with virgin littermates. Flow cytometric analyses revealed an increase in renal T cells after pregnancy, and cytokine analysis revealed a systemic proinflammatory shift. Finally, the NO:ET-1 ratio was reduced. These results demonstrate that the link between the maternal syndrome of superimposed preeclampsia and postpartum risk of chronic kidney disease could involve both immune system activation and dysregulation of the NO:ET-1 balance.

Protective Effects of Wheat Peptides against Ethanol-Induced Gastric Mucosal Lesions in Rats: Vasodilation and Anti-Inflammation

“…PGE2 enhances mucosal blood flow and angiogenesis, and it accelerates epithelial wound repair and mucosal healing [ 49 ]. Endothelin (ET)-1 is a strong vasoconstrictor, and the increased release of ET-1 leads to dysregulation of the microcirculation [ 50 ]. It has been reported that ethanol stimulated the release of ET-1 in the gastric mucosa and caused a rapid, time-dependent increase in the level of ET-1 in plasma [ 51 ].…”

Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model

“…In the RUPP model, BP and albuminuria recurred eight weeks after delivery, and no glomerular or tubular damage was detectable [31]. In Dahl salt-sensitive rats, glomerular and tubular injuries were present in female rats eight weeks after giving birth, detected as increased protein levels of nephrin and KIM-1 in the urine [43]. Together with our findings, these results support the evidence that persisting high blood pressure could be a cause for kidney damage observed in humans after preeclamptic pregnancy.…”

Acute kidney injury during pregnancy leads to increased sFlt-1 and sEng and decreased renal T regulatory cells in pregnant rats with HELLP syndrome

“…There are several animal models of preeclampsia and pregnancy-induced hypertension that demonstrate evidence of renal injury including the reduced uterine perfusion pressure [ 28 , 29 ], the Dahl S rat [ 30 , 31 ], the N -nitro- l -arginine methyl ester [ 32 ], and the transgenic renin-angiotensin model of preeclampsia [ 33 ]. There are very few actual models of pregnancy-related AKI.…”