Endothelin-receptor antagonists in uremic cardiomyopathy

Increased endothelin-1 (ET-1) levels were found in patients with chronic re nal failure. These correlate with the severity of renal failure. Patients w ith elevated ET-1 concentrations show an increased cardiovascular mortality . The prevalence of severe left ventricular hypertrophy (LVH) is a very imp ortant factor for survival and morbidity in uremic patients The aim of this study was to assess the protective effect of ET-receptor antagonists in ch ronic uremia. Sprague Dawley rats were subtotally nephrectomized (SNX) and treated either with the endothelin-A- (ETA) receptor antagonist LU302146 or with the unselective ETA/ETB receptor antagonist LU302872 (30 mg/kgbw/day both). After subtotal nephrectomy protein excretion of SNX (130.0 +/- 32.5 mg/24 h) was increased in comparison to the ETA-group (446 +/- 103 mg/24 h) and the ETAB-group (23.2 +/- 37 mg/24 h) vs sham: 115 +/- 19 mg/24 h). Hea rt weight was decreased by the ETA/ETB-receptor antagonist LU302146. Left v entricular contractility was impaired in SNX by about 40%. Treatment with t he ET-receptor antagonists prevented the impairment in left ventricular fun ction. Our study results provide a possible therapeutic approach using ET r eceptor antagonists to reduce cardiac hypertrophy and renal proteinuria. Fu rther human studies are needed to show whether this protection of the heart and kidney might influence the survival and life-expectancy of patients su ffering from chronic renal failure.