Maternal hyperglycemia.

Maternal hyperglycemia and its effects on placental vascular tone and endothelial nitric oxide activity.

Diabetes complicated pregnancies are increasingly prevalent worldwide and are associated with several adverse outcomes including hypertension. Hyperglycemia in the context of diabetes is responsible for vascular dysfunction, which alters vascular tone and blood flow. The molecular signaling by which hyperglycemia perturbs placental vascular function remain ill characterized. Utilizing an ex vivo dual cotyledon, dual perfusion model we investigated the mechanisms of vascular dysfunction that arise from hyperglycemia. Our results indicate that exposure to hyperglycemia directly alters placental vascular tone and promotes exaggerated constriction in response to paracrine signaling. This result was attributed to a significant reduction in endothelial nitric oxide (eNOS) phosphorylation at the serine 1177 residue; an indicator of perturbed nitric oxide synthesis. Altogether our study provides evidence that hyperglycemia enables exaggerated constriction by reducing the potential for NO mediated vasodilation.