Related Experiment Videos
Role of endothelin in heart function in health and disease
L S Golfman1, T Hata, R E Beamish
1Division of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg.
Insights
Endothelins, vasoactive peptides from endothelium, adversely affect heart function by causing vasoconstriction. However, they also have direct positive inotropic and chronotropic effects, with dysfunction linked to pathological conditions.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
Background:
- Endothelins are vasoactive peptides produced by the endothelium.
- They influence coronary blood flow, blood pressure, and cardiac function.
Purpose of the Study:
- To review the literature on endothelins' role in cardiovascular function and dysfunction.
- To elucidate the mechanisms of endothelin action on cardiac cells.
Main Methods:
- Comprehensive literature review.
- Analysis of endothelin's effects on coronary arteries, blood pressure, and cardiac contractility.
- Examination of cellular mechanisms involving endothelin receptors, G-proteins, and intracellular calcium.
Main Results:
- Endothelins cause vasoconstriction, reducing coronary blood flow and increasing blood pressure.
- They exert positive inotropic and chronotropic effects on the myocardium and nodal tissues.
- High concentrations can lead to myocardial hypoxia and dysfunction.
- Specific cellular pathways (e.g., phospholipase C, Ca2+ increase) are involved, but not Na+,K+-ATPase or Ca2+ pumps.
- Elevated plasma endothelins and receptor downregulation are observed in conditions like ischemia-reperfusion, hypertension, and diabetes.
Conclusions:
- Endothelins play a dual role in cardiovascular function, with both detrimental and direct cardiac effects.
- Their mechanisms involve specific receptor-mediated signaling pathways.
- Endothelin dysregulation is implicated in the pathogenesis of various heart dysfunctions.
Abstract:
A comprehensive review of the literature has revealed that endothelins belong to a family of vasoactive peptides which are formed and released from the endothelium. By producing constriction of the coronary arteries and peripheral blood vessels, endothelins are known both to reduce coronary bloodflow and increase blood pressure and thus can be seen to affect heart function adversely. On the other hand, endothelins are capable of producing positive inotropic and chronotropic effects by directly affecting both the myocardium and nodal tissues. Prolonged actions of high concentrations of endothelins can be seen to induce relative hypoxia in the myocardium which will eventually result in heart dysfunction. The mechanisms of actions of endothelin on smooth muscle cells and cardiomyocytes include interaction with endothelin receptors on the cell surface, activation of phospholipase C through G-proteins, and increase in the intracellular concentration of Ca2+ through the increase in phosphoinositol turnover. Endothelins were found to exert no effects on sarcolemmal Na+,K(+)-ATPase, Na(+)-Ca2+ exchange and Ca2+ pump systems nor on the sarcoplasmic reticular Ca2+ pump system and myofibrillar ATPase activities in the rat heart. Marked elevation in the levels of plasma endothelins and down-regulation of endothelin receptors in ischemia-reperfusion injury, hypertension and chronic diabetes indicate a significant role of endothelins in the genesis of heart dysfunction under different pathological conditions.