Serelaxin improves the pathophysiology of placental ischemia in the reduced uterine perfusion pressure rat model of preeclampsia

Preeclampsia is a hypertensive disorder of pregnancy with limited therapeutic options. In healthy pregnancy, relaxin plays an important vasodilatory role to maintain vascular compliance; however, there is currently no preclinical evidence to support the use of relaxin during preeclampsia. Therefore, the goal of this study was to test the hypothesis that recombinant human relaxin-2 (Serelaxin, Novartis, RLX) could reduce mean arterial pressure (MAP) and improve uterine artery resistance index (UARI) and nitric oxide bioavailability and/or decrease prepro-endothelin-1 (PPET-1), soluble fms-like tyrosine kinase-1 (sFlt-1) and tumor necrosis factor (TNF-alpha) in the Reduced Uterine Perfusion Pressure (RUPP) model of preeclampsia. On day 14 of gestation (GD14), pregnant rats were assigned to Normal pregnant (NP), RUPP, RUPP+RLX or NP+RLX groups. Treated rats received RLX at 0.4 ug/h or RLX2 4 ug/h RLX via minipump implanted on GD14. On GD18 carotid arterial catheters were inserted, and on GD19 MAP and tissues were collected. MAP was increased in RUPP rats compared to NP but was lowered with either dose of RLX. UARI and sFlt-1 were significantly improved in both treated RUPP groups. Total circulating nitrate-nitrite improved and placental PPET-1 and TNF-alpha were significantly decreased with the higher dose of RLX. Renal cortex PPET-1 was reduced with both doses of RLX. In conclusion, Serelaxin improved blood pressure, sFlt-1, TNF alpha, UARI and nitric oxide bioavailability and PPET-1 in a rat model of preeclampsia thereby suggesting a potential therapeutic role for RLX in maintaining maternal health and prolonging pregnancy in the face of placental ischemia.