Endothelin-receptor antagonists in uremic cardiomyopathy.
Increased endothelin-1 (ET-1) levels were found in patients with chronic renal failure. These correlate with the severity of renal failure. Patients with elevated ET-1 concentrations show an increased cardiovascular mortality. The prevalence of severe left ventricular hypertrophy (LVH) is a very important factor for survival and morbidity in uremic patients The aim of this study was to assess the protective effect of ET-receptor antagonists in chronic uremia. Sprague Dawley rats were subtotally nephrectomized (SNX) and treated either with the endothelin-A- (ET(A)) receptor antagonist LU302146 or with the unselective ET(A)/ET(B)-receptor antagonist LU302872 (30 mg/kgbw/day both). After subtotal nephrectomy protein excretion SNX (130.0 +/- 22.5 mg/24 h) was increased in comparison to the ET(A)-group (446 +/- 103 mg/24 h) and the ET(AB)-group (23.2 +/- 37 mg/24 h) vs sham: 115 +/- 19 mg/24 h). Heart weight was decreased by the ET(A)/ET(B)-receptor antagonist LU302146. Left ventricular contractility was impaired in SNX by about 40%. Treatment with the ET-receptor antagonists prevented the impairment in left ventricular function. Our study results provide a possible therapeutic approach using ET receptor antagonists to reduce cardiac hypertrophy and renal proteinuria. Further human studies are needed to show whether this protection of the heart and kidney might influence the survival and life-expectancy of patients suffering from chronic renal failure.
Wolf
S C
SC
Medical Clinic III, Institute of Physiology, University of Tübingen, Heidelberg, Germany. 101566.341@compuserve.com
Gaschler
F
F
Brehm
S
S
Klaussner
M
M
Amann
K
K
Risler
T
T
Brehm
B R
BR
D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D009392:Nephrectomy; D011422:Propionates / Q000627:therapeutic use; D011507:Proteinuria / Q000188:drug therapy; D011743:Pyrimidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014511:Uremia / Q000188:drug therapy*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; C113044:LU 224332; D011422:Propionates; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B