Cardiometabolic Outcomes in Dahl Salt-Sensitive Rat Pregnancies: Impact of a Maternal Hypertensive High-Fat Diet

Excessive adiposity and chronic hypertension are major risk factors of preeclampsia, a leading hypertensive disorder of pregnancy. Yet, mechanisms underlying the complex interplay between adiposity, chronic hypertension, and preeclampsia remain incompletely understood, partly due to the limited availability of experimental models that capture these interactions. Herein, we explored maternal cardiometabolic adaptations in high-fat diet (HFD)-fed Dahl Salt-Sensitive rats, an established model of HFD-associated chronic hypertension. We hypothesized that HFD-fed dams would display a superimposed preeclampsia-like phenotype compared to control diet (CD)-fed Dahl Salt-Sensitive females. HFD-fed dams exhibited attenuated gestational weight gain, increased ketogenesis, cardiovascular dysfunction and blunted uteroplacental vascular adaptation to pregnancy. HFD feeding was associated with high blood pressure pre-pregnancy and during most of gestation and lactation. Interestingly, however, both groups displayed a drop in blood pressure during late gestation, with lower blood pressure nadir and lower urine protein excretion in HFD-fed dams. Short-term pregnancy outcomes were largely preserved in HFD-fed dams, including litter size, pup viability, and placental efficiency. Long-term, dietary normalization failed to reverse the hypertensive phenotype of HFD-exposed dams, with blood pressure remaining 10-15 mmHg higher than controls for at least 14 weeks post-weaning. In conclusion, HFD-fed Dahl salt-sensitive females developed chronic hypertension and impaired metabolic and cardiovascular adaptations to pregnancy. Yet, neither CD- nor HFD-fed dams exhibited hallmark preeclampsia features, including late-gestation blood pressure rise, proteinuria, and fetal growth restriction. This model therefore provides a valuable platform to investigate adaptive cardiometabolic mechanisms that may attenuate preeclampsia risk in obese and chronic hypertensive patients.