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Hemodynamic and inotropic effects of endothelin-1 in vivo

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Summary

Endothelin-1 (ET-1) is known to have strong vasoactive properties. Contradictory results have been reported with regard to its inotropic effects.

This study examined the dose-dependent (500, 1000, 2500, 5000 and 10 000 ng ET-1/kg vs. NaCl controls) hemodynamic and inotropic effects of ET-1 in 53 open-chest rats during and after a 7-min infusion. Besides measurements in the intact circulation the myocardial function was examined by isovolumic registrations independent of peripheral vascular effects.

A transient ET-1 induced (500, 1000, 2500, 5000 ng ET-1/kg) decrease of the left ventricular systolic pressure (LVSP) and the mean aortic pressure (AoPmean) was followed by a dose-related rise of these pressures (LVSP: −1%, −1%, +8%, +16% vs. preinfusion values; AoPmean:−11%, +9%, +39%, +52%). Heart rate (HR) was not influenced by ET-1. Due to the dose-dependent decrease of the stroke volume (SV) the cardiac output (CO) was reduced (CO:−8%, −23%, −40%, −50%). After an initial vasodilatation ET-1 elevates the total peripheral resistance (TPR:−1%, +49%, +139%, +215%) dose-dependently. 10000 ng ET-1/kg was a lethal dose resulting in cardiac failure within minutes (low output). Since the maximum of the isovolumic LVSP (peak LVSP) and the corresponding dP/dtmax (peak dP/dtmax) were unchanged under ET-1, the isovolumic measurements do not indicate a positive inotropic effect of ET-1 in vivo in contranst to published results of in vitro experiments.

It may be possible that a direct positive inotropic effect of ET-1 observed in in vitro studies is counterbalanced in vivo by an indirect negative inotropic effect due to the coronar-constrictive effect of ET-1.

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Author notes

  1. M. E. Beyer

    Present address: Medizinische Klinik, Abt. III, Eberhard-Karls-Universität, Otfried-Müller-Straße 10, 72076, Tübingen, FRG

Authors and Affiliations

  1. Medizinische Klinik, Abt. III, Eberhard-Karls-Universität, Otfried-Müller-Straße 10, 72076, Tübingen, FRG

    S. Nerz & H. M. Hoffmeister

  2. Medizinische Klinik, Abt. II, Universität Regensburg, FRG

    B. K. Krämer

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  1. M. E. Beyer
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  4. H. M. Hoffmeister
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Beyer, M.E., Nerz, S., Krämer, B.K. et al. Hemodynamic and inotropic effects of endothelin-1 in vivo. Basic Res Cardiol 89, 39–49 (1994). https://doi.org/10.1007/BF00788676

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  • DOI: https://doi.org/10.1007/BF00788676

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