title: Peripheral Microvascular Vasodilatory Response to Estradiol and Genistein in Women with Insulin Resistance.
abstract: OBJECTIVE
  E2 enhances vasodilation in healthy women, but vascular effects of the phytoestrogen GEN are still under investigation. IR compromises microvascular function. We therefore examined the interaction of E2 , GEN, and IR on microvascular vasodilatory responsiveness.
  
  
  METHODS
  We hypothesized that E2 and GEN increase microvascular vasodilation in healthy women (control, n = 8, 23 ± 2 year, BMI: 25.9 ± 2.9 kg/m2) but not in women with IR (n = 7, 20 ± 1 year, BMI: 27.3 ± 3.0 kg/m2). We used the cutaneous circulation as a model of microvascular vasodilatory function. We determined CVC with laser Doppler flowmetry and beat-to-beat blood pressure during local cutaneous heating (42 °C) with E2 or GEN microdialysis perfusions. Because heat-induced vasodilation is primarily an NO-mediated response, we examined microvascular vasodilation with and without L-NMMA.
  
  
  RESULTS
  In C, E2 enhanced CVC (94.4 ± 2.6% vs. saline 81.6 ± 4.2% CVCmax , p < 0.05), which was reversed with L-NMMA (80.9 ± 7.8% CVCmax , p < 0.05), but GEN did not affect vasodilation. Neither E2 nor GEN altered CVC in IR, although L-NMMA attenuated CVC during GEN.
  
  
  CONCLUSIONS
  Our study does not support improved microvascular responsiveness during GEN exposure in healthy young women, and demonstrates that neither E2 nor GEN improves microvascular vasodilatory responsiveness in women with IR.
authors.affiliation: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Wenner
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Taylor
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.|The John B. Pierce Laboratory, New Haven, Connecticut.|Yale School of Public Health, New Haven, Connecticut, USA.
authors.forename: Nina S
authors.initials: NS
authors.lastname: Stachenfeld
mesh_terms: D000293:Adolescent; D000328:Adult; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D006801:Humans; D007333:Insulin Resistance; D008833:Microcirculation / Q000187:drug effects*; D055806:Microvessels / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004958:Estradiol; D019833:Genistein
keywords: cutaneous microdialysis; estrogen; nitric oxide; phytoestrogens; vascular reactivity