RESUMO
Ischemic injury of the transplanted kidney is one of the causes of reduced graft survival. The purpose of the present experiment was to examine whether hepatocyte growth factor (HGF) would improve acute renal hemodynamic recovery immediately after cold ischemia. Addition of HGF to the preservation solution during 3 h cold ischemia of dog kidney accelerated both recovery of renal blood flow and glomerular filtration rate (GFR). It is suggested that HGF may be useful for preservation of excised kidney for transplantation. As intrarenal arterial infusion of HGF in normal dog kidney had no effects on renal hemodynamics, mechanisms other than direct vasodilator action of HGF appear to be operating in the protection.
Assuntos
Fator de Crescimento de Hepatócito/uso terapêutico , Isquemia/tratamento farmacológico , Rim/irrigação sanguínea , Circulação Renal/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Coleta de Tecidos e Órgãos/métodos , Vasodilatadores/uso terapêutico , Animais , Cães , Taxa de Filtração Glomerular/efeitos dos fármacos , Fator de Crescimento de Hepatócito/farmacologia , Isquemia/fisiopatologia , Transplante de Rim , Traumatismo por Reperfusão/fisiopatologia , Vasodilatadores/farmacologiaRESUMO
The present study was conducted to elucidate the role of oxidative stress and nuclear factor-kappaB (NF-kappaB) in the beneficial effects of angiotensin receptor blockade on obstructive nephropathy. Unilateral ureteral occlusion in rats elicited tubulo-interstitial fibrosis with concomitant macrophage infiltration and increased expression of monocyte chemoattractant protein-1. These changes were accompanied by an induction of renal cortical lipid peroxidation and activation of NF-kappaB. Both an AT(1) antagonist, candesartan, and a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated these changes and to a similar extent. These results suggest that the beneficial effects of angiotensin blockade are mediated by the inhibition of oxidative stress and subsequent NF-kappaB activation in obstructive nephropathy.