Here we investigate the effects of the stable, water-soluble
nitroxyl radical,
TEMPONE, on renal dysfunction and injury caused by
ischemia/reperfusion (I/R) of the rat kidney in vivo.
TEMPONE significantly improved both glomerular and tubular function (serum
urea,
creatinine,
creatinine clearance, and fractional excretion of Na(+)) in a dose-dependent manner and significantly attenuated the
reperfusion-injury associated with I/R (urinary
N-acetyl-beta-D-glucosaminidase,
aspartate aminotransferase, assessment of renal histology).
TEMPONE also markedly reduced the immunohistochemical evidence of the formation of
nitrotyrosine and
poly(ADP-ribose), indicating reduction of nitrosative and oxidative stress, respectively. The latter was reflected in vitro, where
TEMPONE significantly reduced cellular injury of primary cultures of rat renal proximal tubular (PT) cells caused by
hydrogen peroxide in a dose-dependent manner. Importantly, in contrast to its in vivo metabolite
TEMPOL (which also provided protective effects against renal I/R and oxidative stress of PT cells),
TEMPONE reduced renal dysfunction and injury without causing a significant reduction in blood pressure upon administration. These results suggest, for the first time, that
TEMPONE can reduce the renal dysfunction and injury caused by I/R and the injury caused to PT cells by oxidative stress without producing the adverse cardiovascular effects observed when using other
nitroxyl radicals.