Attenuation of endothelin-1 induced vasoconstriction by 17β estradiol is not sustained during long-term therapy in postmenopausal women with coronary heart disease

Jhund, P. S. , Dawson, N., Davie, A. P., Sattar, N. , Norrie, J., O’Kane, K. P.J. and McMurray, J. J.V. (2001) Attenuation of endothelin-1 induced vasoconstriction by 17β estradiol is not sustained during long-term therapy in postmenopausal women with coronary heart disease. Journal of the American College of Cardiology, 37(5), pp. 1367-1373. (doi: 10.1016/s0735-1097(01)01168-8) (PMID:11300448)

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Abstract

OBJECTIVES The goal of this study was to determine the long-term effects of estrogen replacement therapy on the response to endothelin-1 (ET-1) in postmenopausal women with coronary heart disease.<p></p> BACKGROUND It is thought that the vasoconstrictor ET-1 is involved in the development and progression of atherosclerosis. Estrogen replacement may slow the development of atherosclerosis in postmenopausal women.<p></p> METHODS Nineteen of 20 postmenopausal women randomized to either three months of 2 mg oral estradiol or placebo completed the double-blind placebo-controlled protocol. Change in forearm blood flow (FBF) in response to a 60 min brachial arterial infusion of ET-1 (5 pmol/min) was measured before randomization, after one month of randomized therapy and after three months of therapy using venous occlusion plethysmography.<p></p> RESULTS Estrogen treatment had no effect on baseline FBF. Systolic and diastolic blood pressure and heart rate did not change in response to estrogen therapy or ET-1. Before randomization, in response to ET-1, FBF was reduced by −21.9% (mean response over 60 min) in the placebo group and −19.0% in the estradiol group (p = 0.67). After one month of therapy, the response was attenuated in the estrogen group, −10.0%, compared with the placebo group, −23.6 (difference in means 13.6%, 95% confidence interval [0.7%, 26.6%], p = 0.041). After three months of therapy, there was no difference in response between the placebo group, −27.0%, and estrogen group, −30.2% (p = 0.65).<p></p> CONCLUSIONS In postmenopausal women with coronary heart disease, estrogen therapy inhibits the vasoconstrictor response to ET-1 after one month of therapy. This effect is lost after three months of therapy, suggesting that tachyphylaxis to one potentially beneficial action of estradiol develops during chronic treatment.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jhund, Dr Pardeep and Norrie, Prof John and McMurray, Professor John and Sattar, Professor Naveed
Authors: Jhund, P. S., Dawson, N., Davie, A. P., Sattar, N., Norrie, J., O’Kane, K. P.J., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:Journal of the American College of Cardiology
Journal Abbr.:J. Am. Coll. Cardiol.
Publisher:Elsevier
ISSN:0735-1097
ISSN (Online):1558-3597

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