In vivo study of the effect of exogenous estradiol on alpha-adrenoceptor responsiveness of human veins.
Based on previous experimental and epidemiologic findings, we hypothesized that 17 beta-estradiol (E2) could decrease the alpha-adrenergic responsiveness in venous smooth muscle cells (VSMC), thereby decreasing venous tone and contributing to the pathogenesis of varicose veins. To test this hypothesis, the effect of an acute increase in E2 serum concentrations on venous alpha-adrenergic responsiveness to norepinephrine (NE) was studied in young healthy men. We conducted a double-blind, randomized, placebo-controlled cross-over study in 23 male volunteers; 96 +/- 2 h after a single intramuscular (i.m.) injection of 10 mg estradiol valerate or placebo, we quantified the pharmacologic effects of estradiol on alpha-adrenergic responsiveness of superficial hand veins by venous compliance technique (VCT) and on resting blood pressure (BP). After administration of estradiol, E2 serum levels increased 9.97 +/- 7.54-fold (mean +/- 1 SD, p < 0.001) to within the range of premenopausal preovulatory women. No significant difference was observed in mean dose of NE required for half-maximal venoconstriction (ED50, p = 0.224), however, or in the maximal effect of NE (Emax, p = 0.796) after administration of E2 as compared with placebo. A significant difference in diastolic BP (DBP) (p = 0.039) was observed after E2 administration (64.6 +/- 7.7 mm Hg) as compared with placebo (68.3 +/- 7.6 mm Hg); BP (SBP) was not affected (p = 0.786). Our findings do not support the concept that E2 reduces alpha-adrenoceptor responsiveness of SMC in superficial veins.
Jilma
B
B
Department of Clinical Pharmacology, University of Vienna, Austria.
Wolzt
M
M
Wagner
O F
OF
Zweytick
B
B
Monitzer
B
B
Schuller-Petrovic
S
S
Eichler
H G
HG
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006225:Hand / Q000098:blood supply*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D010919:Placebos; D011863:Radioimmunoassay; D014680:Veins / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure
D010919:Placebos; D004958:Estradiol