Haemodynamic effects of valsartan in acute renal ischaemia/reperfusion injury.
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.
Lopau
K
K
Department of Medicine, Division of Nephrology, University Hospital Würzburg, Würzburg, Germany.
Hefner
L
L
Bender
G
G
Heidbreder
E
E
Wanner
C
C
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
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine