Endogenous endothelin maintains coronary artery tone by endothelin type A receptor stimulation in patients undergoing coronary arteriography

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Abstract
OBJECTIVE To examine the contribution of endothelin type A (ETA) receptor stimulation by endogenously generated endothelin-1 (ET-1) to the maintenance of coronary vascular tone in humans. DESIGN Controlled clinical study. SETTING Tertiary cardiovascular referral centre. PATIENTS 14 subjects were studied, seven with normal coronary arteries and seven with coronary artery disease, mean (SEM) age, 53 (2) years. INTERVENTIONS After diagnostic coronary arteriography, BQ-123 (a selective ETA receptor antagonist; 100 nmol/min) in 0.9% saline, was infused into the left coronary artery at a rate of 1 ml/min for 60 minutes. Eight control subjects received saline alone. MAIN OUTCOME MEASURES Blood flow velocity in the left anterior descending coronary artery, measured using a Doppler flow guidewire; coronary arteriography performed at baseline and immediately at the end of the BQ-123 or saline infusion to measure the diameter of proximal and distal left anterior descending coronary artery segments. RESULTS The diameter of the proximal segment increased by 6 (2)%, while that of the distal segment increased by 12 (3)% after BQ-123 (both p < 0.05v baseline). Coronary blood flow increased from 75 (10) to 92 (10) ml/min and coronary vascular resistance decreased from 1.99 (0.36) to 1.44 (0.22) mm Hg/ml/min after BQ-123 (both p < 0.05 v baseline). The response to BQ-123 of patients with and without coronary artery disease was similar. There was no effect of saline in the controls. CONCLUSIONS Endogenously produced ET-1 contributes to the maintenance of basal coronary artery tone in humans by ETA receptor stimulation. The role of ETB receptors remains to be defined.