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Effect of endothelin on normal and diseased human coronary arteries
A H Chester1, G S O'Neil, S P Allen
1National Heart and Lung Institute, Harefield Hospital, Middlesex, UK.
Insights
Endothelin causes dose-dependent contractions in human coronary arteries, potentially contributing to vasospasm and regulating small vessel tone. This peptide plays a role in coronary vascular disorders.
Area of Science:
- Cardiovascular Pharmacology
- Vascular Physiology
Background:
- Endothelin is a potent vasoconstrictor peptide.
- Its role in human coronary artery disorders like vasospasm and atherosclerosis requires further investigation.
Purpose of the Study:
- To investigate the action of endothelin on healthy and diseased human epicardial coronary arteries.
- To assess endothelin's potential role in coronary vascular disorders.
Main Methods:
- Dose-dependent contractions induced by endothelin (10(-10) to 10(-7) mol l-1) were measured in healthy and diseased human epicardial coronary arteries.
- The effect of endothelin on responses to other vasoconstrictors (potassium chloride, U46619, noradrenaline, histamine, 5-HT) was assessed.
- Endothelium denudation was performed on disease-free segments.
Main Results:
- Endothelin induced dose-dependent contractions in both normal and diseased vessels, with greater constriction in healthy vessels at 10(-8) mol l-1.
- Responses were greater in smaller, distal vessel segments.
- Endothelin potentiated the 5-HT response in some patients but not others.
- No significant effect of endothelium denudation was observed.
Conclusions:
- Endothelin's interaction with other vasoconstrictors suggests a mechanism for its involvement in coronary artery vasospasm.
- Endothelin may also regulate vascular tone in the heart's small vessels.
Abstract:
We have examined the action of endothelin on healthy and diseased human epicardial coronary arteries to assess its possible role in coronary vascular disorders such as vasospasm and atherosclerosis. Endothelin (10(-10) mol l-1-10(-7) mol l-1) produced dose-dependent contractions in both normal and diseased vessels. The level of constriction was significantly greatly in healthy vessels at 10(-8) mol l-1 endothelin. A greater response was recorded in smaller, more distal vessel segments, irrespective of the pathology of the tissue. Endothelium denudation of disease-free segments had no significant effect on the response to endothelin. In the presence of a threshold dose of endothelin (10(-9) mol l-1), there was no measurable increase in the tension generated by potassium chloride, the thromboxane-mimetic U46619, noradrenaline and histamine. However, the response to 5-HT showed a large increase in arteries from four patients (440-147%) but slight or no increase in arteries from another three patients. We conclude that the interaction with other vasoconstrictor substances is a possible mechanism whereby endothelin may be involved in coronary artery vasospasm. In addition, endothelin may also be involved in the regulation of vascular tone of the small vessels of the heart.