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[3H]bosentan binding to human coronary artery: functional correlates
M R Dashwood1, M Timm, J R Muddle
1Department of Physiology, Royal Free Hospital School of Medicine, London, England.
Journal of Cardiovascular Pharmacology
|January 1, 1995
Summary
Bosentan, an endothelin-1 (ET-1) antagonist, binds to the human coronary artery and blocks ET-1's constrictive effects. This suggests potential therapeutic use for conditions like atherosclerosis and angina.
Area of Science:
- Cardiovascular Pharmacology
- Endothelin Receptor Antagonism
Background:
- Endothelin-1 (ET-1) plays a role in regulating vascular tone.
- ET-1 is implicated in various cardiovascular pathologies.
Purpose of the Study:
- To investigate the binding characteristics and localization of bosentan in the human coronary artery.
- To assess bosentan's ability to antagonize ET-1 binding and its effects on ET-1-induced coronary artery contraction.
Main Methods:
- In vitro autoradiography using [3H]bosentan to determine binding sites.
- Competition studies with [125I]ET-1 to evaluate bosentan's inhibitory potential.
- In vitro functional assays to measure ET-1-induced coronary artery contraction.
Main Results:
- [3H]Bosentan selectively bound to the tunica media of the human coronary artery.
- Bosentan demonstrated a concentration-dependent inhibition of [125I]ET-1 binding.
- Bosentan effectively antagonized ET-1-induced vasoconstriction in vitro.
Conclusions:
- Bosentan localizes to the human coronary artery media and antagonizes ET-1 binding.
- Bosentan inhibits ET-1-mediated coronary artery constriction in vitro.
- These findings support the potential of bosentan as a therapeutic agent for ET-1-related cardiovascular diseases.