Abstract 576: Relaxin Dit Not Improve Outcome In An Established Preeclamptic Transgenic Rodent Rat Model

Abstract

Preeclampsia affects 5% of pregnancies in industrialized nations and consists of hypertension and proteinuria and characterized by maternal endothelial dysfunction and excessive vascular inflammation starting after 20 weeks of gestation. It represents a major cause for fetal and maternal morbidity and mortality and is an established risk factor for subsequent cardiovascular disease. Relaxin is a peptide hormone secreted by the corpus luteum, circulating in maternal blood during pregnancy. Its administration leads to rapid and sustained vasodilation. We hypothesized that relaxin ameliorates symptoms of preeclampsia in an established rat model. We used rats transgenic for the human angiotensinogen (hAogen) gene and the human rennin (hRen) gene and crossed the strains to produce a model of preeclampsia in the dams. On gestational day 9, hAogen TGR dams (PE rat) were randomly assigned to 2 experimental groups: vehicle (20 mM sodium acetate, pH 5.0,) or relaxin, at a dose of 2 μg/h of relaxin by subcutaneous osmotic minipump (Alzet, Typ 2002) until day 21 of gestation. Mean blood pressure was continuously recorded by radiotelemetry and 24 hour urine samples were collected in metabolic cages at day 18 of gestation. Rats were killed at day 21 of gestation. The fetuses and organs were removed and weighed. Vehicle treated PE rats developed hypertension abruptly at gestational day 13 and had sustained hypertension. Relaxin treatment did not prevent the increase in blood pressure in the last third of pregnancy (MAP on day 16 of gestation: 151.1 ± 2.2 mmHg vehicle vs. 156.6 ± 1.3 mmHg relaxin). Proteinuria was not ameliorated by relaxin (14.6 ± 5.5 mg/d vehicle vs. 20.8 ± 3.8 mg/d relaxin treated group). The number of live fetuses was similar between the groups. In addition, reduced fetal and uteroplacental unit weights were unaffected by relaxin treatment. Furthermore, relaxin treatment had no influence on intra uterine growth restriction, measured by brain to liver ratio (0.795 ± 0.021 vehicle vs. 0.795 ± 0.016 relaxin). Our data demonstrate that relaxin did not ameliorate hypertension, proteinuria or IUGR in a transgenic rat model for preeclampsia.