Endothelin Receptor‐dependent Responses in Overweight/Obese Postmenopausal Women

Abstract

Age‐related weight gain is greater in women compared to men, such that postmenopausal women are more likely to be overweight or obese (OW/Ob). Previous studies have demonstrated that OW/Ob older adults have impaired endothelial function in part due to endothelin‐1 mediated vasoconstriction via the ETA receptor. In addition, our laboratory has recently demonstrated an important role for ETB receptors and its contribution to vascular endothelial dysfunction in postmenopausal women.PURPOSEThe purpose of this study was to test the hypothesis that ETB and ETA receptors contribute to impaired vasodilatory function in OW/Ob postmenopausal women.METHODSFourteen postmenopausal women have completed the study: 8 normal weight (NW; 57±5 years, 22±2 kg/m2) and 6 OW/Ob (57±8 years, 28±3 kg/m2). We measured vasodilatory responses to local heating of the skin (laser Doppler flowmetry) during microdialysis perfusions of lactated Ringer's (Control), ETB receptor blockade (BQ‐788, 300nM), and ETA receptor blockade (BQ‐123, 500 nM). Cutaneous vascular conductance (CVC) was calculated during the plateau phase of local heating (42°C), and normalized to maximal vasodilation achieved by perfusion of sodium nitroprusside (28mM) and heating to 43°C. A two‐way ANOVA with post hoc Bonferroni correction was performed to compare the impact of weight on vascular responses to ETA and ETB mediated vasodilation compared to control. Data are presented as mean ± standard deviation.RESULTSETB receptor blockade increased vasodilation in NW women (Control: 88±4 vs. BQ‐788: 94±4 %CVC max; P=0.03), whereas ETA receptor blockade did not significantly alter vasodilation (BQ‐123: 88±3 %max CVC; P>0.90 vs. Control). In OW/Ob, both ETB and ETA blockade increased vasodilation (Control: 89±4 vs. BQ‐788: 95±4, BQ‐123: 94±5 %max CVC; P<0.05). Furthermore, the vasodilatory response to ETA receptor blockade was greater in OW/Ob compared to NW (P=0.03).CONCLUSIONThese preliminary data suggest that while blockade of ETB receptors improves vasodilatory function in postmenopausal women, there is a larger contribution of ETA receptors impacting endothelial function in OW/Ob postmenopausal women.Support or Funding InformationSupported by: NIH GRANT P20 GM 113125 and AHA 16SDG30700015This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.