Endothelin has been implicated in the pathogenesis of ischemic heart disease and congestive heart failure. The aims were to quantify endothelin type A (ETA) and type B (ETB) receptor mRNA levels in human coronary arteries from patients with ischemic heart disease, congestive heart failure and controls using real-time polymerase chain reaction (real-time PCR). In addition, the suitability of organ culture as a model mimicking endothelin receptor changes in cardiovascular disease was evaluated by in vitro pharmacology and real-time PCR. Endothelin ETA and ETB receptor mRNA levels were significantly higher in arteries from patients with ischemic heart disease (0.23+/-0.04 and 0.35+/-0.06) as compared to congestive heart failure (0.09+/-0.02 and 0.07+/-0.01) and controls (0.08+/-0.02 and 0.08+/-0.01). After organ culture, the endothelin ETB receptor mRNA levels were elevated, and the sarafotoxin 6c-induced vasoconstriction was more efficacious. Increased endothelin receptor activity may contribute to the increased vascular tone and development of atherosclerotic disease in ischemic heart disease in man.