Estrogen induces nitric oxide-mediated vasodilation of human mammary arteries in vitro.
Human internal mammary arteries (IMA) are relatively protected from atherosclerosis. Estrogen plays a protective role in cardiovascular disease. It causes in vitro and in vivo vasodilatation, but the mechanisms are contradictory. To investigate the in vitro vasomotor effect of estrogen on IMA and the role of endothelium, we studied 30 IMA segments harvested from 10 men during coronary artery bypass grafting surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, and smoking were excluded. Twenty IMA rings had intact endothelium ((+)Endo) and 10 rings were denuded of endothelium ((-)Endo). Vasomotor response of each ring was expressed as the percentage of maximal response to norepinephrine (NE). Acetylcholine (10(-8)-10(-5) M) given to (+)Endo and (-)Endo rings induced vasorelaxation of 72 +/- 30.4% and vasoconstriction of 48.5 +/- 20.1%, respectively. 17-Beta-estradiol (10(-8)-10(-5) M) given after maximal precontraction with NE induced marked relaxation in (+)Endo (80.9 +/- 39.2%), but no significant vasomotor effect in (-)Endo rings (P < 0.0001). Vasorelaxation to 17-beta-estradiol (10(-6) M) in (+)Endo rings was 64.5 +/- 18.4 and 8.6 +/- 8.4%, before and after 15-min treatment with nitric oxide synthase inhibitor, L-nitroarginine methyl ester, respectively (n = 14, P < 0.0001). Tamoxifen (10(-6) M) decreased 17-beta-estradiol (10(-7) M)-induced relaxation by 71%. In conclusion, 17-beta-estradiol induces endothelium-dependent NO-mediated vasodilation of human mammary arteries in vitro. This response is mediated through estrogen receptors.
Nechmad
A
A
Department of Cardiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Merin
G
G
Schwalb
H
H
Shimon
D V
DV
Borman
J B
JB
Milgalter
E
E
Mosseri
M
M
D000368:Aged; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D004958:Estradiol