A NEW MODEL OF RENAL MICROVASCULAR ENDOTHELIAL INJURY

Although the importance of injury with consequent activation of endoth elium is well-recognized in diseases affecting the glomerular endothel ial cell (GEN), research on GEN injury in vivo has been hampered by th e lack of adequate animal models. Here we report the establishment and characterization of a new GEN injury model in rats. This model was in duced by selective renal artery perfusion with anti-GEN IgG and result ed in the severe acute renal failure with marked platelet deposition a nd development of a thrombotic microangiopathy involving glomeruli. Pe ritubular capillary endothelial cells were also damaged that was assoc iated with severe tubular necrosis. Although the glomerular changes we re severe, half of the glomeruli recovered by day 10, while interstiti al changes remained throughout our observation time course. Proliferat ion of GEN was observed during the recovery phase. An increased expres sion of endothelial nitric oxide synthase in GEN was also observed, an d may be an adaptive mechanism to counteract the thrombosis and ischem ia. This model should be useful to investigate the pathophysiology of renal microvascular diseases and the mechanisms of GEN injury, activat ion and recovery in vivo.