Estrogen supplementation attenuates vasoconstrictor responses to norepinephrine and decreases total body norepinephrine spillover in perimenopausal women.

Estrogens are reported to provide protection against the development of cardiovascular disease in women. The mechanisms underlying these effects are not well defined. Reports on the effects of estrogen on blood pressure are conflicting. We hypothesized that estrogen might influence the release of, and/or responses to, norepinephrine (NE). We measured NE spillover to plasma, and forearm vasoconstrictor responses to NE in 12 perimenopausal women before and after 8 weeks of estrogen supplementation (estradiol valerate 2 mg daily, N=7) or placebo (n=5). Total body and forearm NE spillover were measured using radiotracer methodology. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Estrogen supplementation decreased systolic (127±3.6 to 114±4 mmHg), and diastolic (81±1 to 71±2 mmHg) blood pressure. Forearm vasoconstrictor responses to NE (25, 50 and 100 ng/min) were attenuated following estrogen supplementation (decrease in FBF pre-estrogen 16±4, 24±4, 34±4 vs decrease post-estrogen 3±1, 11±5, 13±2%), but not following placebo. Total body NE spillover decreased significantly following estrogen supplementation (pre: 528±110, post: 355±45 ng/min, p<0.05), but not following placebo. Forearm spillover of NE was unchanged by either estrogen or placebo. Thus, estrogen supplementation in perimenopausal women reduces blood pressure, and may exert its effects in part by selectively attenuating vasoconstrictor responses to NE. Estrogen supplementation also decreases total body spillover of NE without influencing regional spillover in the forearm. The relation of these changes to estrogen-induced cardiovascular protection remains to be determined.