Selective Upregulation of Cardiac Endothelin System in Patients With Ischemic but Not Idiopathic Dilated Cardiomyopathy: Endothelin-1 System in the Human Failing Heart

ABSTRACTOnly scarce information is available on the activity and modifications of the cardiac endothelin (ET)–1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro–ET-1 (ppET-1), ET-converting enzyme-1, and ETA and ETB receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription–polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ETA and ETB receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P