Cardiopulmonary effects of endothelin-1 in man

David G. Kiely, Robert I. Cargill, Allan D. Struthers, Brian J. Lipworth

    Research output: Contribution to journalArticle

    54 Citations (Scopus)

    Abstract

    Objectives: Endothelin-1 levels are elevated in a number of conditions characterised by impaired cardiovascular performance and abnormal vasoconstriction such as congestive cardiac failure and primary and secondary pulmonary hypertension. The aim of the present study was to assess the effects of the vasoconstrictor peptide endothelin-1 on pulmonary and systemic haemodynamics and cardiovascular performance in normal man. Methods: Ten healthy male volunteers were studied on two occasions in a randomised, double-blind, placebo-controlled, cross-over study and received systemic infusions of either endothelin-1 (0.75, 1.5 and 3 pmol · kg-1 · min-1 for 30 min each) or saline placebo. Systemic and pulmonary haemodynamic parameters were monitored non-invasively by pulsed-wave Doppler, as were parameters of left and right ventricular diastolic filling and inotropic state. Effects on renin-angiotensin and natriuretic peptide system activity were also measured. Results: Endothelin-1 infusion produced dose-related falls in heart rate, stroke volume and cardiac output. Systemic vascular resistance (SVR) increased from 1156 ± 57 to 1738 ± 115 dyn · s · cm-5, and total pulmonary vascular resistance (TPR) increased from 142 ± 12 to 329 ± 22 dyn · s · cm-5. Endothelin-1 caused significant impairment of left and right ventricular diastolic filling, even at a low dose which had no pulmonary or systemic pressor effects. Electromechanical and Doppler acceleration indices of inotropic state were also significantly impaired. Activity of the renin-angiotensin system was suppressed by endothelin-1 whilst plasma levels of atrial natriuretic peptide (ANP) were unchanged. Conclusions: Thus, in addition to systemic and pulmonary pressor effects our results suggest that endothelin-1 impairs overall cardiovascular performance by causing diastolic dysfunction and acting as a negatively inotropic agent. These effects were associated with compensatory changes in the renin-angiotensin system.
    Original languageEnglish
    Pages (from-to)378-386
    Number of pages9
    JournalCardiovascular Research
    Volume33
    Issue number2
    DOIs
    Publication statusPublished - 1997

    Fingerprint

    Endothelin-1
    Lung
    Renin-Angiotensin System
    Vascular Resistance
    Hemodynamics
    Placebos
    Endothelin-3
    Natriuretic Peptides
    Angiotensins
    Atrial Natriuretic Factor
    Vasoconstrictor Agents
    Vasoconstriction
    Renin
    Cardiac Output
    Stroke Volume
    Cross-Over Studies
    Healthy Volunteers
    Heart Failure
    Heart Rate
    Peptides

    Cite this

    Kiely, David G. ; Cargill, Robert I. ; Struthers, Allan D. ; Lipworth, Brian J. / Cardiopulmonary effects of endothelin-1 in man. In: Cardiovascular Research. 1997 ; Vol. 33, No. 2. pp. 378-386.
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    abstract = "Objectives: Endothelin-1 levels are elevated in a number of conditions characterised by impaired cardiovascular performance and abnormal vasoconstriction such as congestive cardiac failure and primary and secondary pulmonary hypertension. The aim of the present study was to assess the effects of the vasoconstrictor peptide endothelin-1 on pulmonary and systemic haemodynamics and cardiovascular performance in normal man. Methods: Ten healthy male volunteers were studied on two occasions in a randomised, double-blind, placebo-controlled, cross-over study and received systemic infusions of either endothelin-1 (0.75, 1.5 and 3 pmol · kg-1 · min-1 for 30 min each) or saline placebo. Systemic and pulmonary haemodynamic parameters were monitored non-invasively by pulsed-wave Doppler, as were parameters of left and right ventricular diastolic filling and inotropic state. Effects on renin-angiotensin and natriuretic peptide system activity were also measured. Results: Endothelin-1 infusion produced dose-related falls in heart rate, stroke volume and cardiac output. Systemic vascular resistance (SVR) increased from 1156 ± 57 to 1738 ± 115 dyn · s · cm-5, and total pulmonary vascular resistance (TPR) increased from 142 ± 12 to 329 ± 22 dyn · s · cm-5. Endothelin-1 caused significant impairment of left and right ventricular diastolic filling, even at a low dose which had no pulmonary or systemic pressor effects. Electromechanical and Doppler acceleration indices of inotropic state were also significantly impaired. Activity of the renin-angiotensin system was suppressed by endothelin-1 whilst plasma levels of atrial natriuretic peptide (ANP) were unchanged. Conclusions: Thus, in addition to systemic and pulmonary pressor effects our results suggest that endothelin-1 impairs overall cardiovascular performance by causing diastolic dysfunction and acting as a negatively inotropic agent. These effects were associated with compensatory changes in the renin-angiotensin system.",
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    Cardiopulmonary effects of endothelin-1 in man. / Kiely, David G.; Cargill, Robert I.; Struthers, Allan D.; Lipworth, Brian J.

    In: Cardiovascular Research, Vol. 33, No. 2, 1997, p. 378-386.

    Research output: Contribution to journalArticle

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    T1 - Cardiopulmonary effects of endothelin-1 in man

    AU - Kiely, David G.

    AU - Cargill, Robert I.

    AU - Struthers, Allan D.

    AU - Lipworth, Brian J.

    PY - 1997

    Y1 - 1997

    N2 - Objectives: Endothelin-1 levels are elevated in a number of conditions characterised by impaired cardiovascular performance and abnormal vasoconstriction such as congestive cardiac failure and primary and secondary pulmonary hypertension. The aim of the present study was to assess the effects of the vasoconstrictor peptide endothelin-1 on pulmonary and systemic haemodynamics and cardiovascular performance in normal man. Methods: Ten healthy male volunteers were studied on two occasions in a randomised, double-blind, placebo-controlled, cross-over study and received systemic infusions of either endothelin-1 (0.75, 1.5 and 3 pmol · kg-1 · min-1 for 30 min each) or saline placebo. Systemic and pulmonary haemodynamic parameters were monitored non-invasively by pulsed-wave Doppler, as were parameters of left and right ventricular diastolic filling and inotropic state. Effects on renin-angiotensin and natriuretic peptide system activity were also measured. Results: Endothelin-1 infusion produced dose-related falls in heart rate, stroke volume and cardiac output. Systemic vascular resistance (SVR) increased from 1156 ± 57 to 1738 ± 115 dyn · s · cm-5, and total pulmonary vascular resistance (TPR) increased from 142 ± 12 to 329 ± 22 dyn · s · cm-5. Endothelin-1 caused significant impairment of left and right ventricular diastolic filling, even at a low dose which had no pulmonary or systemic pressor effects. Electromechanical and Doppler acceleration indices of inotropic state were also significantly impaired. Activity of the renin-angiotensin system was suppressed by endothelin-1 whilst plasma levels of atrial natriuretic peptide (ANP) were unchanged. Conclusions: Thus, in addition to systemic and pulmonary pressor effects our results suggest that endothelin-1 impairs overall cardiovascular performance by causing diastolic dysfunction and acting as a negatively inotropic agent. These effects were associated with compensatory changes in the renin-angiotensin system.

    AB - Objectives: Endothelin-1 levels are elevated in a number of conditions characterised by impaired cardiovascular performance and abnormal vasoconstriction such as congestive cardiac failure and primary and secondary pulmonary hypertension. The aim of the present study was to assess the effects of the vasoconstrictor peptide endothelin-1 on pulmonary and systemic haemodynamics and cardiovascular performance in normal man. Methods: Ten healthy male volunteers were studied on two occasions in a randomised, double-blind, placebo-controlled, cross-over study and received systemic infusions of either endothelin-1 (0.75, 1.5 and 3 pmol · kg-1 · min-1 for 30 min each) or saline placebo. Systemic and pulmonary haemodynamic parameters were monitored non-invasively by pulsed-wave Doppler, as were parameters of left and right ventricular diastolic filling and inotropic state. Effects on renin-angiotensin and natriuretic peptide system activity were also measured. Results: Endothelin-1 infusion produced dose-related falls in heart rate, stroke volume and cardiac output. Systemic vascular resistance (SVR) increased from 1156 ± 57 to 1738 ± 115 dyn · s · cm-5, and total pulmonary vascular resistance (TPR) increased from 142 ± 12 to 329 ± 22 dyn · s · cm-5. Endothelin-1 caused significant impairment of left and right ventricular diastolic filling, even at a low dose which had no pulmonary or systemic pressor effects. Electromechanical and Doppler acceleration indices of inotropic state were also significantly impaired. Activity of the renin-angiotensin system was suppressed by endothelin-1 whilst plasma levels of atrial natriuretic peptide (ANP) were unchanged. Conclusions: Thus, in addition to systemic and pulmonary pressor effects our results suggest that endothelin-1 impairs overall cardiovascular performance by causing diastolic dysfunction and acting as a negatively inotropic agent. These effects were associated with compensatory changes in the renin-angiotensin system.

    U2 - 10.1016/S0008-6363(96)00219-2

    DO - 10.1016/S0008-6363(96)00219-2

    M3 - Article

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    SP - 378

    EP - 386

    JO - Cardiovascular Research

    JF - Cardiovascular Research

    SN - 0008-6363

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    ER -