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Endothelial modulation of myocardial contraction: mechanisms and potential relevance in cardiac disease

  • A. M. Shah
  • M. J. Lewis
Conference paper

Summary

Recent studies in isolated cardiac preparations and the intact heart demonstrate that the endocardial and coronary vascular endothelium modulate myocardial contractile behaviour and cardiac pump function in a novel manner, mainly by influencing the duration of contraction and the onset of relaxation but without major effect on early systolic contractile characteristics. These effects are mediated by the release of at least two diffusible substances from endothelial cells: a) endothelium-derived relaxing factor (EDRF) which shortens contractile duration by elevating myocardial cyclic GMP, and b) a novel substance, provisionally named “endocardin”, which prolongs contractile duration.

Under physiological conditions these endothelial influences may be particularly important for relaxation and early diastolic filling events in the heart. It is possible that they could influence myocardial growth, interact with other cardiac hormones, and via EDRF inhibit platelet adhesion to endothelial surfaces. The release of the endothelial factors is regulated by stimuli such as circulating neurohumoral substances, increased flow, products of platelet aggregation, and endogenous peptides stored in endothelial cells.

Although experimental evidence is still limited, it seems likely that cardiac endothelium may play an important role in the pathophysiology of cardiac disease, e.g. overload-induced hypertrophy. The endothelium could a) influence the development of phenotype change by modulating and mediating transduction of extrinsic signals, b) contribute to contractile and other abnormalities (especially “diastolic” dysfunction) because of loss or impairment of its normal function, and c) be uniquely amenable to therapeutically useful pharmacological manipulation.

Key Words

Endothelium EDRF myocardial contraction diastole cardiac hypertrophy 

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Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt 1992

Authors and Affiliations

  • A. M. Shah
    • 1
    • 3
  • M. J. Lewis
    • 2
  1. 1.Cardiff Cardiovascular Sciences Research Group, Departments of CardiologyUniversity of Wales College of MedicineCardiffWales (UK)
  2. 2.Pharmacology & TherapeuticsUniversity of Wales College of MedicineCardiffWales (UK)
  3. 3.Dept. of CardiologyUniversity of Wales College of MedicineCardiffUK

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