(Circulation. 2000;102:445.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Chronic 17ß-Estradiol Replacement Increases Nitric Oxide–Mediated Vasodilation of Guinea Pig Coronary Microcirculation
From the Department of Obstetrics/Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore.
Correspondence to Loren P. Thompson, PhD, Department of Obstetrics/Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201. E-mail lthompso{at}ummc001.ummc.umaryland.edu
Background—Estrogen is cardioprotective of the coronary circulation by mechanisms incompletely understood. This study determined the effect of chronic 17ß-estradiol replacement on dilator responses to acetylcholine and sodium nitroprusside of the isolated coronary microcirculation.
Methods and Results—Adult female guinea pigs were ovariectomized,
and a 21-day-release pellet containing 0.0, 0.1, 0.25, 0.5, or 1.0 mg
17ß-estradiol was implanted subcutaneously. Serum estradiol
concentrations ranged from 3.9 to 74.9 pg/mL, increasing with the dose
of estradiol. After 19 to 20 days, the animals were euthanized, and
their hearts were removed and perfused with buffer at constant flow on
an isolated heart apparatus. Both perfusion pressure and
contractile force were measured in prostaglandin
F2
–constricted hearts. Vasodilation to the cumulative
addition of the endothelium-dependent agonist
acetylcholine (10-9 to
10-5 mol/L) and the nitric oxide (NO) donor
sodium nitroprusside (10-9 to
10-5 mol/L) was measured before and after NO
synthesis inhibition by nitro-L-arginine (LNA,
10-4 mol/L). Baseline coronary
resistance was unaltered by estradiol, although LNA increased
resistance in estradiol-treated hearts more than in ovariectomized
controls. Chronic 17ß-estradiol increased sensitivity (measured by
-log EC50 values) but not maximal response to
acetylcholine compared with ovariectomized controls. Differences were
abolished by LNA at all doses of estradiol. Sodium
nitroprusside–induced dilation was unaffected by estradiol
replacement.
Conclusions—Chronic 17ß-estradiol replacement, at doses producing hormone levels within the physiological range, enhances dilator sensitivity of the coronary microcirculation through enhanced NO production by the endothelium, independent of changes in NO sensitivity of the vascular smooth muscle. Thus, estradiol enhances NO production as a protective mechanism of the coronary microcirculation.
Key Words: acetylcholine • hormones • nitric oxide • vasodilation • endothelium
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