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