Short-term administration of estrogen and vascular responses of atherosclerotic coronary arteries.
OBJECTIVE
This experiment sought to determine the effect of short-term administration of estrogen on endothelium-dependent dilation in the coronary arteries of 13 surgically postmenopausal female cynomolgus monkeys.


BACKGROUND
Long-term estrogen replacement therapy prevents impaired endothelium-dependent dilation of atherosclerotic coronary arteries in postmenopausal female monkeys. However, it remains unclear whether this action of estrogen is due to long-term effects on plasma lipids and atherogenesis or to direct short-term effects on the endothelium.


METHODS
The monkeys consumed an atherogenic diet for 18 months after bilateral ovariectomy. Vascular responses were measured just before euthanasia and necropsy. Dextrose in water (control), acetylcholine, 10(-6)M, and nitroglycerin were infused for 2.5 min each both before and 20 min after intravenous injection of 54 ng ethinyl estradiol.


RESULTS
Quantitative coronary angiography revealed that the arteries constricted (-17 +/- 3%) in response to intracoronary infusion of acetylcholine before estrogen treatment but dilated (+5 +/- 3%) 20 min after intravenous injection of ethinyl estradiol (p less than 0.05). Coronary arteries dilated in response to nitroglycerin both before and after administration of estrogen (p greater than 0.05). Vascular responses of coronary arteries, both before and after administration of estrogen, were not associated with variation in plasma lipid concentrations, blood pressure, heart rate or plaque size.


CONCLUSIONS
Estrogen affects endothelium-dependent coronary dilation within 20 min of administration and may have rapid direct effects on the vascular endothelium.
Williams
J K
JK
Comparative Medicine Clinical Research Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1040.
Adams
M R
MR
Herrington
D M
DM
Clarkson
T B
TB
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D008252:Macaca fascicularis; D005996:Nitroglycerin / Q000494:pharmacology; D010052:Ovariectomy; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D008076:Cholesterol, HDL; D004997:Ethinyl Estradiol; D002784:Cholesterol; D005996:Nitroglycerin; D000109:Acetylcholine