Nephrol Dial Transplant (2004) 19: 83-94
© ERA–EDTA 2003; all rights reserved
Original Article
Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure
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dica Jovovi2-Stanojevi2-Miri3-Adanja3-Lipkovski4ko B. Vojvodi51Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, 6Departamento de Bioquímica Clinica, Hospital Universitario de Salamanca, 37007 Salamanca, Spain, 2Laboratory of Cardiovascular Physiology, Institute for Medical Research, 4Institute of Pathology and 5Institute of Biophysics, Medical School, 11001 Belgrade and 3Institute of Nuclear Medicine–Clinical Center, Belgrade, Yugoslavia
Correspondence and offprint requests to: José Miguel López Novoa, MD, PhD, Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Avenida Campo Charro s/n, 37007 Salamanca, Spain. Email: jmlnovoa{at}usal.es
Background. The relative roles of endothelin (ET)-1 and angiotensin (ANG) II in post-ischaemic acute renal failure (ARF) have not been fully established so far. With the aim of contributing to this goal, we assessed in this study the effect of ANG II and ET-1 blockade on the course of post-ischaemic-ARF.
Methods. Anaesthetized Wistar rats received i.v. either bosentan (a dual ET receptor antagonist; 10 mg/kg body weight) or losartan [ANG II type 1 (AT1) receptor antagonist; 5 or 10 mg/kg body weight] or both, 20 min before, during and 20 min after ischaemia. Rats in the control group received the vehicle via the same route. Survival and renal function were monitored up to 8 days after the ischaemic challenge, while haemodynamic parameters were measured 24 h after ARF.
Results. Our results demonstrate that bosentan treatment has a more beneficial effect on experimental ARF than losartan. The survival rate was remarkably higher in bosentan-treated rats than in both rat groups treated with losartan. In the ARF group treated with bosentan, renal blood flow (RBF) was increased by 129% in comparison with the untreated ARF group, whereas in the losartan-treated ARF groups, RBF was only 
35 or 38% higher than in control ARF rats. The glomerular filtration rate was markedly higher in bosentan-treated rats than in all other ARF groups on the first and second day after ischaemia. Tubular cell injury was less severe in bosentan-treated rats than in the control ARF rats, but in losartan-treated groups it was similar to that in the ARF group. Concurrent blockade of both ET and AT1 receptors did not improve ARF because this treatment induced a marked decrease in blood pressure.
Conclusions. These results suggest that ET-1 blockade is more efficient in improving the early course of post-ischaemic renal injury than ANG II inhibition, and that blockade of ET-1 might be effective in prophylaxis of ischaemic ARF.
Keywords: acute renal failure; bosentan; ischaemia–reperfusion injury; losartan; rats
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