Regulation of vascular function during pregnancy: A novel role for the pregnane X receptor.

摘要

The mechanisms underling pregnancy-induced alterations in maternal vascular function are unclear. Progesterone metabolites, which are elevated during pregnancy, are potent ligands for the Pregnane X Receptor (PXR) a nuclear receptor which regulates cytochrome P450 (CYP) enzyme expression. CYP epoxygenases produce epoxyeicosatrienoic acids (EETs), known vasodilators. We hypothesized, therefore, that PXR contributes to the regulation of vascular tone during pregnancy by enhancing CYP mediated relaxation. PXR and Cyp2c29 expression was shown in mouse mesenteric arteries by RT-PCR. Assessment of vascular function by wire myography showed blunted vasoconstriction and enhanced vasorelaxation in pregnant wildtype mice. However, these adaptations were absent in PXR knockout mice, indicating that PXR mediates the development of altered vascular function during pregnancy. Inhibition of CYP epoxygenases and EETs caused negligible reductions in vasoconstriction, however this pathway may still regulate vasorelaxation. Further investigation of these PXR mediated mechanisms will contribute significantly to our understanding of pregnancy-induced alterations in vascular function.