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(-8)mol/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)-10(2)mmol/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 mediated constriction in PrEC (P=0.003). ETBR-inhibition attenuated endothelium-dependent vasodilation responses to 100mmol/L ACh (P=0.04) and local heat (P=0.003) in HC but increased vasodilation (ACh: P= 0.01; local heat: P=0.03) in PrEC. Women who have had preeclampsia demonstrate augmented vasoconstrictor sensitivity to ET-1, mediated by altered ETBR signaling. Furthermore, altered ETBR function contributes to diminished endothelium-dependent dilation in previously preeclamptic women.
Pharmacology, Toxicology and Pharmaceutical Science
1
3%
Nursing and Health Professions
1
3%
Other
3
10%
Unknown
15
50%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 December 2017.
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#31,228,352
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#3,186
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#437,399
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#30
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