Related Experiment Videos
Role of endothelin in spontaneous phasic contraction of human coronary arteries
P H Dagassan1, M Clozel, V Breu
1Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Insights
Endothelin (ET) plays a key role in spontaneous phasic contractions (SPCs) of isolated human coronary arteries. Blocking endothelin receptors with antagonists like BQ-123 or bosentan abolished these contractions, confirming ET
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Isolated human coronary arteries exhibit spontaneous phasic contractions (SPCs).
- The role of endothelin (ET) in these contractions is not fully understood.
Purpose of the Study:
- To investigate the involvement of endothelin (ET) in spontaneous phasic contractions (SPCs) of isolated human coronary arteries.
Main Methods:
- Utilized endothelium-denuded human coronary artery rings from patients with coronary artery disease.
- Administered ETA receptor antagonist BQ-123 and mixed ET receptor antagonist bosentan.
- Applied exogenous endothelin-1 (ET-1) at various concentrations.
Main Results:
- Spontaneous phasic contractions (SPCs) were observed in isolated human coronary artery rings.
- BQ-123 and bosentan abolished these contractions.
- Exogenous ET-1 increased SPC amplitude and induced contractions, even after blockade.
Conclusions:
- Endothelin (ET) significantly contributes to spontaneous phasic contractions (SPCs) in isolated human coronary arteries.
- ET receptor antagonists effectively inhibit ET-mediated SPCs.
- ET signaling is crucial for maintaining coronary artery tone.
Abstract:
Isolated human coronary arteries are known to develop spontaneous phasic contractions (SPCs). The goal of the present study was to assess the role of endothelin (ET) in these contractions. Endothelium-denuded rings from left anterior descending (LAD) coronary arteries of patients with coronary artery disease (CAD; n = 3) undergoing cardiac transplantation developed SPCs within 1-2 h. The contractions were abolished by the ETA receptor antagonist BQ-123 or the mixed ET receptor antagonist bosentan (1 and 3 microM), whereas the contractions persisted for several hours in control rings. Exogenous ET-1 (10 pM) increased the amplitude of SPCs and initiated SPCs in rings that did not exhibit SPCs. Higher concentrations of ET-1 (> or = 1 nM) were able to re-induce SPC in rings in which SPCs had been abolished by BQ-123 or bosentan. These results suggest that ET plays an important role in spontaneous phasic contractions of isolated human coronary artery rings.