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

P. S. Jhund, N. Dawson, A. P. Davie, N. Sattar, John David Norrie, K. P. J. O'Kane, J. J. V. McMurray

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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.

    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.

    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.

    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).

    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. (J Am Coll Cardiol 2001;37:1367-73) (C) 2001 by the American College of Cardiology.

    Original languageEnglish
    Pages (from-to)1367-1373
    Number of pages6
    JournalJournal of the American College of Cardiology
    Volume37
    Issue number5
    DOIs
    Publication statusPublished - 2001

    Keywords

    • ESTROGEN REPLACEMENT
    • NITRIC-OXIDE
    • VASODILATION
    • PROGESTERONE
    • ARTERIES
    • FAILURE
    • FLOW
    • ATHEROSCLEROSIS
    • ACETYLCHOLINE
    • BRADYKININ

    Cite this

    Attenuation of endothelin-1 induced vasoconstriction by 17 beta 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, John David; O'Kane, K. P. J.; McMurray, J. J. V.

    In: Journal of the American College of Cardiology, Vol. 37, No. 5, 2001, p. 1367-1373.

    Research output: Contribution to journalArticle

    Jhund, P. S. ; Dawson, N. ; Davie, A. P. ; Sattar, N. ; Norrie, John David ; O'Kane, K. P. J. ; McMurray, J. J. V. / Attenuation of endothelin-1 induced vasoconstriction by 17 beta estradiol is not sustained during long-term therapy in postmenopausal women with coronary heart disease. In: Journal of the American College of Cardiology. 2001 ; Vol. 37, No. 5. pp. 1367-1373.
    @article{75e776af293c4ecdbbee3964cf6cd979,
    title = "Attenuation of endothelin-1 induced vasoconstriction by 17 beta estradiol is not sustained during long-term therapy in postmenopausal women with coronary heart disease",
    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.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.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.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).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. (J Am Coll Cardiol 2001;37:1367-73) (C) 2001 by the American College of Cardiology.",
    keywords = "ESTROGEN REPLACEMENT, NITRIC-OXIDE, VASODILATION, PROGESTERONE, ARTERIES, FAILURE, FLOW, ATHEROSCLEROSIS, ACETYLCHOLINE, BRADYKININ",
    author = "Jhund, {P. S.} and N. Dawson and Davie, {A. P.} and N. Sattar and Norrie, {John David} and O'Kane, {K. P. J.} and McMurray, {J. J. V.}",
    year = "2001",
    doi = "10.1016/S0735-1097(01)01168-8",
    language = "English",
    volume = "37",
    pages = "1367--1373",
    journal = "Journal of the American College of Cardiology",
    issn = "0735-1097",
    publisher = "Elsevier USA",
    number = "5",

    }

    TY - JOUR

    T1 - Attenuation of endothelin-1 induced vasoconstriction by 17 beta estradiol is not sustained during long-term therapy in postmenopausal women with coronary heart disease

    AU - Jhund, P. S.

    AU - Dawson, N.

    AU - Davie, A. P.

    AU - Sattar, N.

    AU - Norrie, John David

    AU - O'Kane, K. P. J.

    AU - McMurray, J. J. V.

    PY - 2001

    Y1 - 2001

    N2 - 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.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.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.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).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. (J Am Coll Cardiol 2001;37:1367-73) (C) 2001 by the American College of Cardiology.

    AB - 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.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.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.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).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. (J Am Coll Cardiol 2001;37:1367-73) (C) 2001 by the American College of Cardiology.

    KW - ESTROGEN REPLACEMENT

    KW - NITRIC-OXIDE

    KW - VASODILATION

    KW - PROGESTERONE

    KW - ARTERIES

    KW - FAILURE

    KW - FLOW

    KW - ATHEROSCLEROSIS

    KW - ACETYLCHOLINE

    KW - BRADYKININ

    U2 - 10.1016/S0735-1097(01)01168-8

    DO - 10.1016/S0735-1097(01)01168-8

    M3 - Article

    VL - 37

    SP - 1367

    EP - 1373

    JO - Journal of the American College of Cardiology

    JF - Journal of the American College of Cardiology

    SN - 0735-1097

    IS - 5

    ER -