title: Estrogen supplementation decreases norepinephrine-induced vasoconstriction and total body norepinephrine spillover in perimenopausal women.
abstract: Estrogens are reported to provide protection against the development of cardiovascular disease in women, but the mechanisms underlying these effects are not well defined. We hypothesized that estrogen might reduce neural cardiovascular tone. We therefore studied responses to exogenous norepinephrine and norepinephrine spillover in 12 perimenopausal women randomized to 8 weeks of estrogen supplementation (estradiol valerate, 2 mg daily, n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not influence blood pressure or heart rate. Total body and forearm norepinephrine spillover were measured by radiotracer methodology. Forearm vasoconstrictor responses to norepinephrine (25, 50, and 100 ng/min) were attenuated after estrogen supplementation (P=.002). Vasoconstrictor responses to angiotensin II (8, 16, and 32 ng/min) were unchanged postestrogen. There was a significant reduction in total body spillover of norepinephrine after estrogen supplementation (pre-estrogen, 700+/-152; postestrogen, 439+/-150 ng/min; P<.05), but there was no change after placebo. Total body clearance and forearm spillover of norepinephrine were unchanged by either estrogen or placebo. Estrogen supplementation also significantly decreased both systolic and diastolic blood pressures. Therefore, estrogen supplementation in perimenopausal women selectively attenuates vasoconstrictor responses to norepinephrine and reduces total body norepinephrine spillover, which is an index of sympathetic neural activity.
authors.affiliation: Alfred and Baker Medical Unit and Menopause Clinic, Baker Medical Research Institute and Alfred Hospital, Melbourne, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Sudhir
authors.forename: M D
authors.initials: MD
authors.lastname: Elser
authors.forename: G L
authors.initials: GL
authors.lastname: Jennings
authors.forename: P A
authors.initials: PA
authors.lastname: Komesaroff
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008593:Menopause / Q000502:physiology*; D008657:Metabolic Clearance Rate; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology*; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects; D014280:Triglycerides / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D001786:Blood Glucose; D004966:Estrogens, Conjugated (USP); D014280:Triglycerides; D000804:Angiotensin II; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D002784:Cholesterol; D009638:Norepinephrine