Gender and nitric oxide-mediated vasodilation in humans

Background: We compared forearm vasodilator responses between females and males after administration of compounds that stimulate nitric oxide (NO) release, act as NO donors, or are NO-independent. Methods and results: We studied nine premenopausal females and nine age-matched males. Forearm blood flow (FBF) was measured with plethysmography. Graded doses of the endothelial-dependent vasodilators acetylcholine and bradykinin and the endothelial-independent vasodilator sodium nitroprusside were given via a brachial artery catheter to the non-dominant arm. Reactive hyperemia was measured as an index of NO-independent vasodilation. In females estradiol levels were greater, and serum triglycerides were lower, but cholesterol was similar to that of males. FBF responses to all doses of the three drugs were similar to 30% less in females. Females had smaller forearms and lower peak FBF during reactive hyperemia. Blood flow responses to the drugs as a fraction of the peak reactive hyperemia values were similar in females and males. In the females, but not in the males, FBF responses to all three drugs and reactive hyperemia correlated with estradiol levels. Conclusions: The smaller FBF responses in females were likely due to smaller forearm volume and muscle mass. Estradiol levels are associated with both NO-mediated and non-NO-mediated dilator responses in females.