Impact of Obesity on ETB Receptor-Mediated Dilation in Mid-life Premenopausal Women

Obesity is a major contributing factor to cardiovascular disease. Declines in vascular endothelial function in overweight/obese (OW/Ob) older adults have been linked to Endothelin-A receptor (ETAR) dysfunction. In women, increased adiposity and weight gain commonly occur in midlife, beginning around the fourth decade. We have previously shown that Endothelin-B receptor (ETBR) mediates vasodilation in young premenopausal women (PRE), an effect that is lost with aging/menopause. However, it remains unclear whether adiposity impacts ETBR-mediated dilation in midlife PRE. The purpose of this study was to test the hypothesis that ETBR-mediated vasodilation is lost in OW/Ob midlife PRE compared to normal weight (NW) PRE. Twenty-six midlife PRE (age 35-50yrs) participated in the study: 13 NW (45±5yrs) and 13 OW/Ob (46±3 yrs). We measured cutaneous vasodilatory responses to local heating of 42°C using Laser Doppler Flowmetry during microdialysis perfusions of lactated Ringer’s (control) and ETBR blockade (BQ-788, 300nM). Brachial blood pressure was measured throughout. Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flow / mean arterial blood pressure during the plateau phase of local heating and normalized to maximal vasodilation achieved by perfusion of sodium nitroprusside (28mM) and heating to 43°C. By design, the OW/Ob group had higher BMI (NW: 23±2kg/m2 vs. OW/Ob: 28±2kg/m2, P< 0.01). No differences in vasodilation at the control site was observed between NW and OW/Ob women (NW: 85.9±11.1% vs. OW/Ob: 82.5±13.3%; P=0.504). However, blockade of the ETB-R decreased vasodilation in NW (77.1±16.9%) but enhanced vasodilation in OW/Ob (87.5±9.9%, P=0.048). Blood pressure was similar between the groups (P>0.10). These findings suggest that in midlife PRE women, adiposity is associated with a loss of ETBR-mediated vasodilation. Additional work is needed to understand if adiposity-related shifts in endothelin receptor function contribute to vascular dysfunction in women as they age. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.