title: Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure.
abstract: 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 (AT(1)) 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 approximately 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 AT(1) 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.
authors.affiliation: Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Avenida Campo Charro s/n, 37007 Salamanca, Spain.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Jerkić
authors.forename: Zoran
authors.initials: Z
authors.lastname: Miloradović
authors.forename: Durddica
authors.initials: D
authors.lastname: Jovović
authors.forename: Nevena
authors.initials: N
authors.lastname: Mihailović-Stanojević
authors.forename: Juan Vicente Rivas
authors.initials: JV
authors.lastname: Elena
authors.forename: Danica
authors.initials: D
authors.lastname: Nastić-Mirić
authors.forename: Gordana
authors.initials: G
authors.lastname: Grujić-Adanja
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez-Barbero
authors.forename: Jasmina
authors.initials: J
authors.lastname: Marković-Lipkovski
authors.forename: Srećko B
authors.initials: SB
authors.lastname: Vojvodić
authors.forename: Marta Vicens
authors.initials: MV
authors.lastname: Manero
authors.forename: Marta Pérez
authors.initials: MP
authors.lastname: Prieto
authors.forename: José Miguel
authors.initials: JM
authors.lastname: López-Novoa
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology* / Q000628:therapy; D000804:Angiotensin II / Q000187:drug effects / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000628:therapy; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D013449:Sulfonamides; D000804:Angiotensin II; D019808:Losartan; D000077300:Bosentan