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 I/R 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 1 h left renal artery clamping followed by 30min reperfusion with blood. In another group, kidneys were isolated and, after transferral to the perfusion system, the perfusion pump was turned off for 1 h, followed by 30min reperfusion with Krebs' solution. BN 52021 or its vehicle dimethylsulphoxide (DMSO) was administered 20min 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.
Uluoglu
C
C
Gazi University, Faculty of Medicine, Department of Pharmacology, Bahcelievler-Ankara, Turkey.
Timlioglu
O
O
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D046934:Ginkgolides; D066298:In Vitro Techniques; D007511:Ischemia / Q000150:complications; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D007783:Lactones / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010649:Phenylalanine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011817:Rabbits; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014665:Vasodilator Agents; C039351:platelet activating factor receptor; D009599:Nitroprusside; D010649:Phenylalanine; C045856:ginkgolide B; D000109:Acetylcholine