Estrogen improves acetylcholine-induced but not metabolic vasodilation in biological males

We have previously shown that chronic estrogen therapy improves endothelium -dependent vasodilation in the resistance vessels of biological males. Whet her this is nitric oxide (NO) mediated and whether estrogen improves metabo lic vasodilation is unknown. Resting forearm blood flow (FBF), ACh-induced vasodilation, and functional hyperemic blood flow (exercise) were assessed before and after the inhibition of NO with NG-monomethyl-L-arginine (L-NMMA ) in 15 male-to-female transsexuals prescribed estrogen and in 14 age-match ed males. Resting FBF was similar in the two groups and was similarly (P = 0.44) but significantly reduced by 48% after infusion of L-NMMA (P < 0.0001 ). The ACh dose-response relationship was shifted upward and to the left in the transsexual compared with the male group (P < 0.01). After the inhibit ion of NO, however, the difference in the ACh dose-response curve between t he two groups was abolished (P = 0.15). Peak functional hyperemic blood flo w was similar for the two groups (P = 0.94). L-NMMA produced a significant (P < 0.01) but similar (P = 0.64) reduction in peak hyperemia in the two gr oups. The volume of blood repaid to the forearm 1 and 5 min after exercise was also reduced by L-NMMA (P < 0.0001); however, there were no differences between the two groups. This suggests that ACh-mediated NO-dependent vasod ilation may be more sensitive to the effects of chronic estrogen than exerc ise-induced vasodilation. Long-term estrogen does not appear to improve exe rcise-induced metabolic vasodilation in biological males, despite the fact that NO contributes to this process.