Evidence of Endothelin‐B Receptor Dysfunction in Obesity

Abstract

BackgroundThe endothelin system has been identified as a key regulator of vascular function and is comprised of two opposing receptors; a constricting A‐receptor (ETAR) and dilating B‐receptor (ETBR). Dysregulation of the ETBR and obesity both independently contribute to vascular endothelial dysfunction. However, whether obese individuals exhibit ETBR dysfunction has yet to be determined. Thus, this study sought to test the hypothesis that microvascular ETBR dysfunction is present in obesity compared to normal weight individuals.MethodsIntradermal microdialysis assessments were completed on 13 individuals (9 men; 4 women; age range: 19–38 years old). Participants were recruited according to BMI: lean (BMI ≤ 24.9 kg/m2; n = 6) or overweight/obese (BMI ≥ 25.0 kg/m2; n = 7). Two microdiaylsis fibers were inserted into the dermal layer of the right forearm where cutaneous blood flow was measured using laser speckle contrast imaging. ETBR function was determined two ways: 1) by a seven dose incremental perfusion of ET‐1 (10−20–10−8 M) combined with the selective ETAR antagonist, BQ‐123 (750 nM), and 2) by a seven dose incremental perfusion of ET‐3 (10−17–10−11 M), the isoform that has ETBR selectivity at low doses. The dose response area under the curve (AUC) for cutaneous vascular conductance was calculated for each individual.ResultsThe AUC for the ET‐1 + BQ‐123 dose response was significantly (p=0.02 reduced in the overweight/obese group (AUC = 157.0 ± 11.0 AU) when compared to the lean group (AUC = 221.8 ± 41.1 AU). The AUC for the ET‐3 dose response tended (p=0.21) to be lower in the overweight/obese group (AUC = 155.2 ± 8.5 AU) compared to the lean group (AUC = 191.3 ± 46.4 AU).ConclusionThese data suggest that ETBR function is impaired in obesity compared to normal weight individuals. The reduced ETBR function may contribute to the observed prevalence of vascular endothelial dysfunction in obesity; however, this hypothesis warrants further investigation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.