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Endothelial cell regulation of contractility of the heart
1Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6085, USA.
Insights
Cardiac endothelial cells release substances like endothelin that regulate heart muscle contraction. These substances adjust heart muscle efficiency and power based on oxygen levels.
Area of Science:
- Cardiovascular physiology
- Endothelial cell biology
- Cardiac muscle mechanics
Background:
- Endocardial and coronary vascular endothelial cells influence cardiac myocyte contraction.
- Endothelin is a key substance regulating cardiac contraction, while other down-regulating substances remain unidentified.
- The release of these regulatory substances is linked to tissue oxygen tension (pO2).
Purpose of the Study:
- To investigate the role of endothelial cells in regulating cardiac myocyte contraction.
- To identify the substances released by endothelial cells that modulate cardiac function.
- To understand the relationship between oxygen tension and the release of regulatory substances.
Main Methods:
- Analysis of substances released by endocardial and coronary vascular endothelial cells.
- Measurement of isometric force and actomyosin ATPase activity in cardiac myocytes.
- Investigation of the effects of endothelin and beta-adrenergic agonists on cardiac function.
Main Results:
- Endothelin was identified as a major, possibly sole, up-regulating substance.
- Tissue oxygen tension influences the concentration of both up- and down-regulating substances.
- Endothelin increases isometric force and decreases actomyosin ATPase activity, enhancing energy conversion efficiency.
- Beta-adrenergic agonists increase ATPase activity via an endothelial cell-dependent pathway, optimizing for power over efficiency.
Conclusions:
- Two distinct endothelial cell-dependent systems regulate cardiac contractile efficiency.
- The endothelin system optimizes cardiac contraction for efficiency.
- The beta-adrenergic-mediated system optimizes cardiac contraction for power.
Abstract:
Endocardial and coronary vascular endothelial cells release substances that modify the contraction of cardiac myocytes. The major and possibly the sole up-regulating substance is endothelin. Several down-regulating substances are secreted, but none has yet been specifically identified. The relative amounts of up- and down-regulating substances are related to tissue oxygen tension. As pO2 rises, the concentration of up- and down-regulating substances, respectively, increases and decreases. Endothelin increases isometric force and decreases actomyosin ATPase activity thus increasing the economy of conversion of chemical to hydrodynamic energy. Beta-adrenergic agonists increase ATPase activity through an endothelial cell-dependent mechanism, leading to decreased economy. Therefore, two endothelial cell-dependent systems exist for regulating contractile efficiency: One involving endothelin appears to optimize the contraction for efficiency; the other, the beta-adrenergic-mediated system, optimizes for power.