Nephrol Dial Transplant (2001) 16: 1592-1597
© 2001 European Renal Association-European Dialysis and Transplant Association
Haemodynamic effects of valsartan in acute renal ischaemia/reperfusion injury
Department of Medicine, Division of Nephrology, University Hospital Würzburg, Würzburg, Germany
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 receptor1 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 SpragueDawley 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-receptor1 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.
Keywords: acute renal failure; angiotensin II receptor antagonist; L-arginine; NO system; valsartan
Correspondence and offprint requests to: Kai Lopau MD, Department of Medicine, Division of Nephrology, University Hospital Würzburg, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany.