The Role of Maternal Protein Intake During Late Gestation on Placental Vascular Function

Abstract

Global nutrient restriction or excess can influence umbilical hemodynamics in sheep fetuses (Chapter 2). We hypothesized that a specific component of the diet, namely maternal metabolizable protein (MP), would alter placental function. When MP restriction during late gestation occurs, we hypothesized that there would be a decrease in the sensitivity to bradykinin (BK) of the placental vascular arteries. In experiment 1, ewes received one of three isocaloric dietary treatments during late gestation: MP60: 60% of MP requirements; MP80: 80% of MP requirements; and MP100: 100% of the MP requirements on a dry matter basis from day 100 to 130 of gestation. In experiment 1, fetal and placental mass were not affected by dietary treatment; however, placental function was altered by a maternal diet low in protein. Ewes not meeting MP requirements during late gestation had fetal placental arteries that were more sensitive to BK-induced vasorelaxation; therefore we reject our hypothesis for experiment 1. In order to understand the mechanism of BK-induced vasodilation in the placental arteries, experiment 2 was designed. We hypothesized that MP level would alter the mechanism of BK-induced vasorelaxation in placental arteries. In experiment 2, ewes received one of three isocaloric dietary treatments during late gestation: MP60: 60% of MP requirements; MP100: 100% of the MP requirements; and MP140: 140% of MP requirements from day 100 to 130 of gestation. Maternal protein level during gestation did not impact the mechanism of BK-induced vasodilation; therefore we reject our hypothesis for experiment 2. However, the maternal and fetal placental vessels responded to BK through different iv mechanisms. In maternal placental arteries, pathways involving endothelium-derived hyperpolarizing factors (EDHF) and nitric oxide (NO) were responsible for BK-induced vasodilation, while the prostacyclin (PGI2) pathway did not greatly contribute to BKinduced vasodilation. The fetal placental arteries responded to BK through a mechanism that does not involve EDHF, NO, or PGI2, indicating that BK-induced vasorelaxation of the fetal placental arteries may be mediated through an unclassified EDHF-like pathway. It is important to realize the maternal and fetal placental arteries may respond to BKinduced vasodilation through different pathways when considering possible therapeutics for compromised pregnancies.