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Microvascular endothelial function in lean versus obese women with polycystic ovary syndrome: role of the endothelin B receptor
Author(s) -
Usselman Charlotte W,
Taylor Hugh S,
Stachenfeld Nina S
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.691.5
Subject(s) - polycystic ovary , medicine , endocrinology , vasodilation , endothelial dysfunction , nitric oxide , endothelin 1 , endothelin receptor , microdialysis , obesity , receptor , insulin resistance , central nervous system
Polycystic ovary syndrome (PCOS) affects 10% of women and is associated with myriad cardiovascular risk factors, including obesity and endothelial dysfunction. PCOS is also associated with elevated levels of plasma endothelin‐1 (ET‐1), one of several circulating indicators of endothelial injury and dysfunction. Women with PCOS have reduced vasodilatory responses to ET‐1 as mediated through the endothelin receptor subtype B (ETBR). We hypothesized that impairments in ETBR‐dependent and independent vasodilation are more severe in obese than in lean women with PCOS. We tested 3 lean (age 30 ± 6 y; BMI 23 ± 1 kg/m 2 ) and 3 obese (33 ± 5 y; 36 ± 4 kg/m 2 ) women diagnosed with PCOS according to the Rotterdam criteria. We assessed cutaneous vascular conductance (CVC) with laser Doppler flowmetry during intradermal microdialysis perfusions of ET‐1 (1, 3, 4, 5, and 7 pmol) with either lactated Ringer's solution, ETBR inhibition (BQ‐788), or nitric oxide inhibition (L‐NMMA). Dose‐response curves (%CVCmax) as a function of the log concentration of ET‐1 demonstrated reduced vasodilatory responses in lean PCOS (logEC 50 0.61 ± 0.07) relative to obese PCOS (logEC 50 0.52 ± 0.47). Inhibition of ETBR decreased the ET‐1‐induced vasodilation in both lean (i.e., logEC 50 0.66 ± 0.11) and obese (logEC 50 0.62 ± 0.21) groups. Contrary to our hypothesis, this inhibition was two‐fold greater in obese PCOS women, indicating a greater role for ETBR‐induced vasodilation under basal conditions relative to lean PCOS. Conversely, nitric oxide inhibition had little effect in either lean (logEC 50 0.61 ± 0.32) or obese PCOS women (logEC 50 0.54 ± 0.18) compared to ET‐1 alone. Our data suggest that impairments to endothelial function are more severe in lean than obese women with PCOS, and that ETBR plays an important role in this potentially adverse cardiovascular outcome. Support or Funding Information Supported by The John B. Pierce Laboratory and the American Heart Association (15POST24990003).