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Background-Atherosclerotic coronary arteries are prone to constriction but the underlying causes are incompletely understood. We tested the hypothesis that endothelin-1 (ET-1), a potent vasoconstrictor, contributes to the heightened tone of atherosclerotic human coronary arteries. Methods and Results-In 8 patients with coronary artery disease (CAD) and 8 patients with angiographically smooth coronary arteries (normal), we infused BQ-123, an antagonist of the ET A receptor, into a major coronary artery (infused artery) at 40 nmol/min for 60 minutes. The infused artery in the CAD patients contained a Ͼ50% stenosis. Using quantitative angiography, we compared the dilation of the infused artery with another, noninfused coronary artery. To estimate the magnitude of the contribution of ET-1 to coronary tone, we compared the dilation to BQ-123 with that elicited by intracoronary nitroglycerin (200 g). BQ-123 induced significant dilation in the normal arteries (7.3% at 60 minutes, PϽ0.001 versus noninfused arteries) and a greater dilation in the CAD arteries (16.3% at 60 minutes, PϽ0.001 versus infused normal arteries). The dilation at stenoses was particularly pronounced (21.6% at 60 minutes, PϽ0.001 versus infused CAD arteries). Compared with the dilation from nitroglycerin, ET-1 contributed to 39% of the coronary tone in normal arteries, 74% of tone in CAD arteries, and 106% of tone at stenoses (PϽ0.01). Conclusions-ET-1 accounts for nearly all the resting tone in atherosclerotic coronary arteries, especially at stenoses.Inhibitors of ET-1, by relieving constriction, may significantly lessen the hemodynamic significance of coronary stenoses and thereby reduce myocardial ischemia.

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Cardiac transplantation has emerged as a valuable therapy for various end-stage cardiac disorders. Cardiac allograft vasculopathy (CAV), an unusually accelerated and diffuse form of obliterative coronary arteriosclerosis, determines long-term function of the transplanted heart. Cardiac allograft vasculopathy is a complicated interplay between immunologic and nonimmunologic factors resulting in repetitive vascular injury and a localized sustained inflammatory response. Dyslipidemia, oxidant stress, immunosuppressive drugs, and viral infection appear to be important contributors to disease development. Endothelial dysfunction is an early feature of CAV and progresses over time after transplantation. Early identification of CAV is essential if long-term prognosis is to be improved. Annual coronary angiography is performed for diagnostic and surveillance purposes. Intravascular ultrasound is a more sensitive diagnostic tool for early disease stages and has revealed that progressive luminal narrowing in CAV is in part due to negative vascular remodeling. Because of the diffuse nature of CAV, percutaneous and surgical revascularization procedures have a limited role. Prevention of CAV progression is a primary therapeutic goal.