Effect of Estrogen Replacement Therapy on Endothelial Function of Peripheral Resistance Artery in Postmenopausal Women - Comparison of Normotensive Subjects and Hypertensive Patients -
To determine whether endothelial dysfunction is demonstrable in the forearm circulation of hypertensive postmenopausal women (HPW) compared with normotensive postmenopausal women (NPW), and to evaluate the effects of long-term estrogen replacement therapy (ERT) on endothelial function in the HPW and NPW, we randomized both HPW and NPW into groups with ERT for 12 weeks (n=26 and 10) or with placebo (n=8 and 6), respectively. Forearm blood flow was measured using strain-gauge plethysmography during reactive hyperemia to test endothelium-dependent vasodilation, and after sublingual nitroglycerin administration to test endothelium-independent vasodilation. Basal forearm blood flow was similar in NPW and HPW. Forearm blood flow in HPW during reactive hyperemia was significantly less than that in NPW. Increases in forearm blood flow after nitroglycerin were similar in the two groups. ERT lowered LDL cholesterol and increased estradiol and HDL cholesterol; no change occurred in the placebo group. Changes in these parameters evoked by ERT were similar in HPW and NPW. Basal blood pressures, heart rate, forearm blood flow, or body weight was not changed by ERT. After 12 weeks of ERT, maximal forearm blood flow response during reactive hyperemia increased significantly from 18.4 ± 2.6 to 28.6 ± 3.4 mL/min/100 mL tissue (p<.05) in HPW and from 26.5 ± 1.9 to 30.9 ± 3.9 mL/min/100 mL tissue (p<.05) in NPW, but it was not changed by placebo. The improvement of reactive hyperemia after ERT was significantly greater in HPW than in NPW (56 ± 8 vs. 17 ± 3%, P<.05). Changes in forearm blood flow after sublingual nitroglycerin administration were similar before and after 12 weeks of ERT. These findings suggest that continued ERT improves endothelial dysfunction in postmenopausal women, and that HPW show endothelial dysfunction which can be improved by ERT via the mechanism other than beneficial effects on lipid metabolism.