Objective-To examine the contribution of endothelin type A (ET A ) 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 ET A 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 < 0.05 v 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 eVect of saline in the controls. Conclusions-Endogenously produced ET-1 contributes to the maintenance of basal coronary artery tone in humans by ET A receptor stimulation. The role of ET B receptors remains to be defined. (Heart 2000;84:176-182) Keywords: endothelins; arteries; blood flow; coronary circulation; angiographyThe endothelins are a family of 21 amino acid peptides with potent and characteristically sustained vasoconstrictor and vasopressor actions.1 Endothelin-1 (ET-1) is the predominant isopeptide generated by the vascular endothelium.2 ET-1 binds to at least two receptors. The ET A receptor appears to be the major one, causing vasoconstriction in arteries, while the ET B receptor mediates the release of endothelium dependent vasodilator substances and is also present in some resistance and capacitance arteries, where it can contribute to vasoconstriction.3 ET-1 may play a role in the pathophysiology of several conditions associated with vasoconstriction, including chronic heart failure, hypertension, Raynaud's disease, and renal failure.3 4 Recently described inhibitors of endothelin converting enzyme and endothelin receptor antagonists may therefore have therapeutic potential as vasodilator drugs in these conditions. Endogenous production of ET-1 contributes importantly to the maintenance of basal peripheral vascular tone 5 and blood pressure 6 in healthy volunteers, mainly through an eVect on ET A receptors. In contrast, the main eVect of endogenous ET-1 on ET B receptors in resistance arteries appears to be vasodilatation. ET-1 constricts human epicardi...