Endothelium-dependent vasodilation in the isolated rabbit kidney following in vivo and in vitro ischaemia and reperfusion:: effects of antagonizing platelet activating factor (PAF)

Renal ischaemia-reperfusion (I/R) is a pathological condition occurring frequently after transplantation and acute renal failure. A mediator thought to play a role in the disturbed haemodynamics of VR is platelet activating factor (PAF). We studied endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) vasorelaxant responses and the effect of BN 52021, a PAF antagonist, in the isolated perfused rabbit kidney after in vivo and in vitro I/R. Anaesthetized rabbits underwent right nephrectomy and Ih left renal artery clamping followed by 30 min reperfusion with blood. In another group, kidneys were isolated and, after transferral to the perfusion system, the pel-fusion pump was turned off for 1 h followed by 30 min reperfusion with Krebs' solution. BN 52021 or its vehicle dimethylsulphoxide (DMSO) was administered 20 min before left renal artery occlusion or turning off the pump. Although in vitro I/R did not influence ACh-induced responses, in vivo I/R caused a decrease which was prevented by BN 52021. SNP-induced responses did not change in in vitro I/R and decreased only at lower concentrations in in vivo I/R, whereby pretreatment with BN 52021 did not offer any protection. It is concluded that in vivo I/R diminishes ACh-induced endothelium-dependent vasodilation, possibly via PAF and blood components, whereas SNP-induced endothelium-independent vasodilation was not altered by in vivo and in vitro ischaemia in the isolated rabbit kidney.