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Endothelial modulation of myocardial contraction: mechanisms and potential relevance in cardiac disease
1Department of Cardiology, University of Wales College of Medicine, Cardiff, UK.
Insights
The cardiac endothelium modulates heart function by releasing factors that influence contraction and relaxation duration. These endothelial-derived factors may play a key role in cardiac disease and offer therapeutic potential.
Area of Science:
- Cardiovascular Physiology
- Endothelial Biology
- Cardiac Pharmacology
Background:
- The cardiac endothelium and endocardium influence myocardial contractility and pump function.
- These effects primarily impact contraction duration and relaxation onset, not early systolic characteristics.
Purpose of the Study:
- To elucidate the mechanisms by which cardiac endothelium modulates myocardial function.
- To identify the key substances released by endothelial cells and their roles.
- To explore the potential implications of endothelial function in cardiac disease pathophysiology.
Main Methods:
- Studies utilized isolated cardiac preparations and intact heart models.
- Investigated the effects of diffusible substances released from endothelial cells.
- Examined the regulation of endothelial factor release by various stimuli.
Main Results:
- Endothelial cells release endothelium-derived relaxing factor (EDRF), which shortens contraction duration via cyclic GMP elevation.
- A novel substance, "endocardin," prolongs contractile duration.
- These factors are crucial for physiological relaxation and diastolic filling, and their release is regulated by neurohumoral substances, flow, and platelet products.
Conclusions:
- Cardiac endothelial factors are vital for normal cardiac function, particularly relaxation and diastolic filling.
- Impaired endothelial function may contribute to cardiac abnormalities, especially diastolic dysfunction and hypertrophy.
- The cardiac endothelium presents a promising target for pharmacological interventions in cardiovascular diseases.
Abstract:
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.