Dichotomous estradiol and genistein effects on cutaneous endothelium‐dependent vasodilation in women with and without insulin resistance (678.6)

17β‐estradiol (E2) cardioprotection in women includes endothelial dependent dilation (EDD), but this E2 effect is not consistent in insulin resistant women (IR). Genistein (GEN, a phytoestrogen structurally similar to E2) effects on EDD are unclear. We hypothesized E2 and GEN improve cutaneous EDD in healthy women [C, n=8, 23 (6) yr, BMI 25.0 (8.0), AUC insulin 6111 (1368) µUI/ml] but not IR [n=6, 20 (2) yr, BMI 27.3 (8.4), AUC insulin 140006 (4020) µUI/ml]. We measured cutaneous vascular conductance (CVC) with laser Doppler flowmetry during local 42°C heating with E2 or GEN skin microdialysis infusions, each with and without the eNOS inhibitor L‐NMMA; nitroprusside was then infused with 44°C heating to induce CVCmax. In C, E2 enhanced EDD [93.4 (5.8) %max, 85.0 (12.2) %max for E2, saline P<0.05], with no GEN effect [84.5 (22.2) %max], and L‐NMMA reduced EDD [81.9 (21.6) %max, GEN 73.2 % (29.1) %max P<0.05). In IR, E2 and GEN did not affect EDD [93.5 (5.5), 93.6 (5.2), 97.4 (13.0), saline, E2, GEN]; L‐NMMA reduced EDD with GEN [67.1 (18.7) %max P<0.05] but not E2 [90.5 (5.5)]. E2 and GEN did not enhance EDD in women with IR in contrast to healthy women. However, NO contributes to EDD in both groups. Grant Funding Source : Supported by National Institutes of Health HL109882