Haemodynamic effects of valsartan in acute renal ischaemia/reperfusion injury

Background. Acute deterioration of renal function is an important side-effe ct of angiotensin-converting enzyme (ACE) inhibitors, especially if accompa nied by other nephrotoxic events. Angiotensin II receptor, blockers (ARB) a re thought to have fewer side-effects on renal perfusion and function. We e xamined the effects of valsartan (VAL) on kidney function as well as the co ntribution of the nitric oxide (NO) system in a rat model of ischaemic acut e renal failure (ARF). Methods. ARF was induced by 40 min of clamping of both renal arteries in fe male Sprague-Dawley rats. Renal haemodynamic and tubular parameters were de termined during post-ischaemic infusion of vehicle, VAL, VAL and the NO-syn thase substrate L-arginine, and VAL together with inhibition of NO synthase s (NOS) by L-NMMA. Results. Clamping induced acute renal failure with marked decreases in glom erular filtration rate (GFR) and renal plasma flow (RPF) accompanied by a r ise in renal vascular resistance (RVR) and fractional sodium excretion. Val sartan caused a slight but significant improvement of GFR and RPF without f ull recovery of renal function and caused a lowering of RVR and tubular sod ium loss. L-arginine-co-administration had no additive beneficial effect. V alsartan-induced changes were not significantly depressed by unspecific inh ibition of NOS. Conclusions. Inhibition of the angiotensin II-receptor(1) diminishes the de leterious effects of ischaemia and reperfusion on glomerular function and o n the renal microcirculation. An involvement of the NO system could not be demonstrated.