Prenatal Arginase Changes and Fetal Oxygenation

ABSTRACT

We have previously reported that developmentally, lung arginase expression and activity are highest during fetal life. Prenatally oxygenation and gas exchange is dependent on uterine blood flow and placental function. As gestation advances, the systemic vascular resistance decreases and uterine blood flow progressively increases to accommodate the fetal needs. The factors accounting for the pregnancy-associated vasodilation are not fully understood. Arginases compete with nitric oxide synthases for L-arginine as a substrate and their tissue expression and activity are known to modulate nitric oxide-dependent vascular tone. Hypothesizing that the pregnancy-induced vasodilation is mediated by a decrease in arginase activity, we evaluated mesenteric arterial and uterine tissue from nonpregnant and late gestation rats. A statistically significant (P<0.01) decrease in arginase activity was documented in both tissues from pregnant animals, when compared with nonpregnant rats. The mesenteric arterial endothelium-dependent vasodilation of pregnant rats was significantly increased (P<0.01) when compared with vessels from nonpregnant animals. Arginase inhibition abrogated this difference. Distinct changes in arginases activity were present in the mother and fetus. Whereas in the fetal lung vascular tissue arginase activity was upregulated to maintain a high pulmonary vascular resistance, the opposite occurred in the maternal systemic circulation where a decrease in vascular tissue arginase activity enhanced uterine blood flow.

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