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Am J Physiol Renal Physiol 282: F1140-F1149, 2002. First published December 18, 2001; doi:10.1152/ajprenal.00329.2001
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Vol. 282, Issue 6, F1140-F1149, June 2002

Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells

Sergey V. Brodsky1,*, Tokunori Yamamoto2,*, Tetsuhiro Tada3, Byungsoo Kim1, Jun Chen1, Fumihiko Kajiya4, and Michael S. Goligorsky1

1 Departments of Medicine, Physiology, and Biophysics and Program in Bioengineering, State University of New York at Stony Brook, Stony Brook, New York 11794-8152; 2 Departments of Urology and Medical Engineering, Kawasaki Medical School, Okayama 701-0114; and 3 Department of Electrical Engineering, Okayama University of Science, and 4 Department of Cardiovascular Physiology, Okayama University School of Medicine and Dentistry, Okayama 700-0005, Japan

There is accumulating circumstantial evidence suggesting that endothelial cell dysfunction contributes to the "no-reflow" phenomenon in postischemic kidneys. Here, we demonstrated the vulnerability of in vitro, ex vivo, and in vivo endothelial cells exposed to pathophysiologically relevant insults, such as oxidative and nitrosative stress or ischemia. All of these stimuli compromised the integrity of the endothelial lining. Next, we performed minimally invasive intravital microscopy of blood flow in peritubular capillaries, which provided direct evidence of the existence of the no-reflow phenomenon, attributable, at least in part, to endothelial injury. In an attempt to ameliorate the hemodynamic consequences of lost endothelial integrity, we transplanted endothelial cells or surrogate cells expressing endothelial nitric oxide synthase into rats subjected to renal artery clamping. Implantation of endothelial cells or their surrogates expressing functional endothelial nitric oxide synthase in the renal microvasculature resulted in a dramatic functional protection of ischemic kidneys. These observations strongly suggest that endothelial cell dysfunction is the primary cause of the no-reflow phenomenon, which, when ameliorated, results in prevention of renal injury seen in acute renal failure.

endothelial cell transplantation; renal ischemia; intravital videomicroscopy; erythrocyte velocity; peritubular capillaries

* S. V. Brodsky and T. Yamamoto contributed equally to this study.




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