The influence of exogenous estrogen on microvascular function over time and with preexisting disease in females and males. Response to flow in arterioles from non-CAD adults treated with (n = 4) or without (n = 57) 100 nM EtOH vehicle control (A) and in the presence of Nω-nitro-l-arginine methyl ester (l-NAME; 100 µM, 30 min; B) (n = 4). C: response to flow in arterioles from CAD/ED adults treated (n = 3) with or without EtOH (n = 30). D: maximal dilation to papaverine in arterioles from non-CAD (n = 68; EtOH, n = 4, P = 0.953) and CAD (n = 27; EtOH, n = 4, P = 0.530) patients treated with or without EtOH. Response to flow in arterioles from females <40 (n = 5; E) and ≥40 (n = 6; F) yr of age treated with 16–20 h of 17β-estradiol (E2), with or without l-NAME (100 µM, 30 min) (< 40 yr, n = 5; ≥40 yr, n = 4) or PEG-catalase (500 U, 30 min) (< 40 yr, n = 4; ≥40 yr, n = 6). G: response to flow in arterioles from females with CAD (n = 6) treated with 16–20 h of E2 (n = 5). H: maximal dilation to 100 µM papaverine in flow in arterioles from females <40 (n = 21; E2, n = 5, P = 0.404) and ≥40 (n = 29; E2, n = 6, P = 0.322) yr of age and those with CAD (n = 6; E2, n = 5, P = 0.258) treated with or without E2 (P > 0.05 between untreated control < 40 yr, ≥40 yr, and CAD). Flow response curves with (non-CAD n = 5; CAD n = 4) or without E2 (non-CAD n = 16; CAD n = 24) treatment in arterioles from non-CAD (I) and CAD (J) males. K: maximal dilation to 100 µM papaverine in arterioles from non-CAD (n = 19; E2, n = 5) and CAD (n = 19; E2, n = 4) males treated with or without E2. Effect of pressure gradient alone was <0.05 in all groups. *P < 0.05: two-way ANOVA treatment effects (A–C, E–G, I, and J) and one-way ANOVA with Fisher’s least significant difference (LSD) test (D, H, and K). Con and Control denote untreated controls. CAD, coronary artery disease; EtOH, ethanol; ED, endothelial dysfunction.