Alterations in Endothelin Type B Receptor Contribute to Microvascular Dysfunction in Women Who Have Had Preeclampsia

Microvascular dysfunction originating during a preeclamptic pregnancy persists postpartum and likely contributes to increased CVD risk in these women. One putative mechanism contributing to this dysfunction is increased vasoconstrictor sensitivity to endothelin-1 (ET-1), mediated by alterations in ET-1 receptor type-B (ETBR). We evaluated ET-1 sensitivity, ETAR and ETBR contributions to ET-1-mediated constriction, and the mechanistic role of  ETBR in endothelium-dependent dilation in vivo in the microvasculature of postpartum women who had preeclampsia (PrEC, n=12) and control women who had a healthy pregnancy (HC, n=12). We hypothesized that 1) PrEC would have a greater vasoconstrictor response to ET-1, and 2) reduced ETBR-mediated dilation. We further hypothesized that ETBR-blockade would attenuate endothelium-dependent vasodilation in HC, but not PrEC. Microvascular reactivity was assessed by measurement of cutaneous vascular conductance responses to graded infusion of ET-1 (10-20-10-8mol/L), ET-1+500nmol/L BQ-123 (ETAR-blockade), and ET-1+300nmol/L BQ-788 (ETBR-blockade), and during graded infusion of acetylcholine (ACh, 10-7-102mmol/L) and a standardized local heating protocol with and without ETBR-inhibition. PrEC had an increased vasoconstriction response to ET-1 (P=0.02). PrEC demonstrated reduced dilation responses to selective ETBR stimulation with ET-1 (P=0.01). ETBR-inhibition augmented ET-1 mediated constriction in HC (P=0.01) but attenuated ET-1 media...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research