Endothelin (ET) is a potent vasoconstrictor peptide implicated in numerous human diseases, including ischemic cardiomyopathy (ICM). ET binds to receptors ETA and ETB. Specific ET receptors were characterized in left atria of patients with end-stage heart failure due to ischernic cardiomyopathy (ICM) (n = 9) and healthy controls (n = 9). Saturation assays revealed a K-d and B-max of 28 8 pM and 87 +/- 22 fmol mg(-1) of protein, respectively, from healthy atria and 50 +/- 9 pM and 162 +/- 19 fmol mg(-1) of protein, respectively, from diseased atria (p < 0.05). For competition studies, we obtained a percentage Of ETA receptors using BQ123, 55%+/- 5 and 66%+/- 4 in healthy and diseased atria, respectively (p < 0.05). The percentage of ETB using BQ3020 was 55%+/- 14 in healthy and 59%+/- 10 in diseased atria. Microautoradiography studies showed a greater number of ET receptors, predominately ETA, existed in the myocardial layer of diseased atria compared with healthy atria. The percentage of occupied area was greater in the endocardium than the epicardium in diseased atria. These results showed an increase in the ETA/ETB receptor system in the failing human heart compared with the non-failing human heart. (C) 2009 Elsevier Ltd. All rights reserved.