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Coronary vasodilation and improvement in endothelial dysfunction with endothelin ET(A) receptor blockade
J P Halcox1, K R Nour, G Zalos
1Cardiology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Md, USA.
Circulation Research
|November 22, 2001
Summary
Endothelin-1 (ET-1) causes vasoconstriction via ET(A) receptors. Inhibiting these receptors improved coronary vascular function and endothelial dysfunction in patients, suggesting therapeutic potential for atherosclerosis.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Endothelin-1 (ET-1) is a peptide causing vasoconstriction through ET(A) receptors.
- Endothelial dysfunction is a key factor in atherosclerosis.
- ET-1's role in human coronary circulation requires further elucidation.
Purpose of the Study:
- To investigate the effect of ET(A) receptor inhibition on human coronary vascular function.
- To determine if ET(A) receptor antagonism improves endothelial dysfunction.
Main Methods:
- Studied 44 patients with atherosclerosis or risk factors.
- Measured epicardial diameter and coronary vascular resistance (CVR) during infusions of acetylcholine (ACH), sodium nitroprusside (SNP), and cold pressor testing.
- Administered intracoronary BQ-123, an ET(A) receptor antagonist.
Main Results:
- BQ-123 increased coronary diameter and decreased CVR, indicating vasodilation.
- Improved ACH-mediated responses, particularly in patients with baseline endothelial dysfunction.
- Reversed cold pressor-induced vasoconstriction, especially in dysfunctional segments.
Conclusions:
- ET-1 acting via ET(A) receptors contributes to coronary vasoconstrictor tone and endothelial dysfunction.
- ET(A) receptor antagonism shows potential for treating endothelial dysfunction and atherosclerosis.
- BQ-123 may enhance cardiac clearance of ET-1, possibly via ET(B) receptors.