Key Points
- To identify the receptor subtypes that mediate endothelin-evoked vasoconstriction across different segments of the human left anterior descending coronary artery.
- Examined isolated proximal and distal segments of human left anterior descending coronary arteries (LAD) for contractile responses to endothelin-1 (ET-1) and endothelin-3 (ET-3).
- Characterized receptor selectivity using pharmacological antagonism with the ETA receptor-selective blocker BQ-123.
- Endothelin-1 was 10 times more potent at inducing contraction in distal segments than in proximal segments, while the potency ratio between ET-1 and ET-3 was approximately 100 across all segments.
- BQ-123 competitively antagonized ET-1-induced contractions in distal segments (pA2 = 7.47) and completely blocked ET-3 responses in both segments.
- BQ-123 produced only partial and non-competitive antagonism against ET-1 in proximal segments, demonstrating that non-ETA receptors also contribute to contraction in proximal vessels.
Structured PICO
PPopulationIsolated segments of the human left anterior descending coronary artery (LAD)
IInterventionEndothelin-1 (ET-1), Endothelin-3 (ET-3), and BQ-123 (ETA receptor antagonist)
OOutcomeContractile responsesurrogate
ETA receptors mediate the contractile response to ET-1 in distal coronary arteries, while other ET receptors are also involved in proximal segments, indicating heterogeneous receptor distribution.