Serelaxin Improves Blood Pressure and Uterine Artery Resistance in the Reduced Uterine Perfusion Pressure (RUPP) Rat Model of Preeclampsia

Abstract

Preeclampsia (PE), new-onset hypertension during pregnancy, is associated with systemic and renal vasoconstriction, as well as fetal growth restriction. Relaxin, vasodilator in humans, plays an important role in maintaining vascular compliance during normal pregnancy; however, there is currently no preclinical evidence to support the use of relaxin during PE. Therefore, we hypothesized that Serelaxin (recombinant human relaxin-2) subcutaneously administered via miniosmotic pump (4 ug/h) days 14-19 of gestation into RUPP rats could improve vascular compliance as a mechanism of reducing uterine artery resistance index (UARI) and improve fetal growth and mean arterial pressure (MAP). Carotid catheters were inserted on day 18. MAP, blood and tissues were collected on day 19. MAP in normal pregnant (NP) rats (n=5) was 106+5, 128+3 in RUPP rats (n=10) and 110+3 mmHg in RUPP+Serelaxin (n=10), p<0.05. Pup weight was reduced with RUPP from 2.3±0.1 in NP (n=5) to 1.9±0.1 g (n=10, p<0.05), and was unchanged in RUPP+Serelaxin (1.9.0±0.1 g, n=10). UARI was 0.66+0.01 in RUPP rats (n=6), but was improved to 0.59+0.02 in RUPP+Serelaxin (n=4), p<0.05. Total nitrate-nitrite concentration was 16.0+2.4 in RUPP rats (n=9), which increased to 25.4+2.5 µM in RUPP+Serelaxin (n=6), p<0.05. In conclusion, Serelaxin improves MAP, UARI and nitric oxide bioavailability. These data suggest an important role for relaxin in maintaining normal blood pressure and vascular compliance during pregnancy which would be helpful to maintain maternal health and prolong pregnancy in the face of placental ischemia.