title: Haemodynamic effects of valsartan in acute renal ischaemia/reperfusion injury.
abstract: BACKGROUND
  Acute deterioration of renal function is an important side-effect of angiotensin-converting enzyme (ACE) inhibitors, especially if accompanied by other nephrotoxic events. Angiotensin II receptor(1) blockers (ARB) are thought to have fewer side-effects on renal perfusion and function. We examined the effects of valsartan (VAL) on kidney function as well as the contribution of the nitric oxide (NO) system in a rat model of ischaemic acute renal failure (ARF).
  
  
  METHODS
  ARF was induced by 40 min of clamping of both renal arteries in female Sprague-Dawley rats. Renal haemodynamic and tubular parameters were determined during post-ischaemic infusion of vehicle, VAL, VAL and the NO-synthase substrate L-arginine, and VAL together with inhibition of NO synthases (NOS) by L-NMMA.
  
  
  RESULTS
  Clamping induced acute renal failure with marked decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) accompanied by a rise in renal vascular resistance (RVR) and fractional sodium excretion. Valsartan caused a slight but significant improvement of GFR and RPF without full recovery of renal function and caused a lowering of RVR and tubular sodium loss. L-arginine-co-administration had no additive beneficial effect. Valsartan-induced changes were not significantly depressed by unspecific inhibition of NOS.
  
  
  CONCLUSIONS
  Inhibition of the angiotensin II-receptor(1) diminishes the deleterious effects of ischaemia and reperfusion on glomerular function and on the renal microcirculation. An involvement of the NO system could not be demonstrated.
authors.affiliation: Department of Medicine, Division of Nephrology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Lopau
authors.forename: L
authors.initials: L
authors.lastname: Hefner
authors.forename: G
authors.initials: G
authors.lastname: Bender
authors.forename: E
authors.initials: E
authors.lastname: Heidbreder
authors.forename: C
authors.initials: C
authors.lastname: Wanner
mesh_terms: D000208:Acute Disease; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007511:Ischemia / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000503:physiopathology; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000503:physiopathology*; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine