Estrogen replacement attenuates resistance artery adrenergic
sensitivity via endothelial vasodilators.
Meyer, Marjorie C., Kathleen Vasquez, George Osol.
Burlington, Vermont, University of Vermont College of Medicine,
Department of Obstetrics and Gynecology
APStracts 3:0528H, 1996.
The objective of this study was to determine whether chronic estrogen
replacement alters adrenergic constriction and endothelium-dependent
dilation in resistance arteries from the rat. Resistance-sized
(<200 [mu]m) mesenteric arteries from castrated female
Sprague-Dawley rats with (E2, 21 day, 0.5 mg pellet) and without
(OvX) estrogen replacement were removed for in vitro study on a
pressurized arteriograph system. Sensitivity to alpha adrenergic
constriction and the role of the endothelium in its modulation, and
of agonist-provoked endothelium dependent relaxation were determined.
Estrogen-treated rats had decreased heart rate, systolic, and
diastolic blood pressure. Arteries from estrogen-replaced rats were
five-fold less sensitive to [alpha]1-adrenergic stimulation with
phenylephrine (EC50:E2= 3.2+/-1.1 [mu]M; OvX=0.6+/-0.2 [mu]M,
p<0.05). This difference was abolished by endothelial
denudation, blockade of cyclooxygenase (1 [mu]M ibuprofen), or nitric
oxide synthase blockade (0.24 mM L-NNA). There was no difference in
muscarinic agonist-provoked relaxation or vascular smooth muscle
sensitivity to prostacyclin or nitroprusside. These results indicate
that estrogen replacement decreases resistance artery adrenergic
sensitivity by increasing the basal release of relaxing factors from
the endothelium. This effect on small artery function may produce
dual cardioprotective effects by decreasing peripheral resistance,
blood pressure, and likelihood of thrombosis.
Received 16 January 1996; accepted in final form 6 December 1996.
APS Manuscript Number H18-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996