Attenuation of renal ischemia/reperfusion injury in inducible
nitric oxide synthase knockout mice.
Ling, Hong, Charles Edelstein, Patricia Gengaro, Xianhong Meng, Scott
Lucia, Mladen Knotek, Adisorn Wangsiripaisan, Yeuxian Shi and Robert
Schrier.
Departments of Medicine1, Surgery 2 and Pathology 3, University of
Colorado Health Sciences Center, Denver, CO 80262, USA
APStracts 6:0111F, 1999.
Renal ischemia/reperfusion (I/R) injury was investigated in iNOS
knockout (iKn) mice. After a 26 min bilateral renal pedicle clamp,
serum creatinine (sCr) concentration (mg/dl) in wild type mice after
24 hr reperfusion were 0.25 ( 0.03 in sham operated controls and 2.3
( 0.38 in ischemia (p < 0.01), and after 48 hr were 0.25 ( 0.03 in
controls and 2.0 ( 0.18 in ischemia (p < 0.01). iKn mice
demonstrated an attenuation of sCr concentration after renal I/R
injury. sCr (mg/dl) after 24 hr reperfusion was 2.3 ( 0.22 in wild
type ischemia and 1.21 ( 0.25 in iKn ischemia (p < 0.05), and after
48 hr was 2.0 ( 0.18 in wild type ischemia and 0.96 ( 0.25 in iKn
ischemia (p < 0.01). Histological scoring of acute tubular necrosis
in iKn mice was decreased compared to wild type controls (0.88 ( 0.2
vs 3.3 ( 0.3, p<0.05). iNOS protein in renal cortex of wild type
mice subjected to renal I/R injury was undetectable up to 48 h.
However, a strong up-regulation of heat shock protein 72 expression
was observed in renal cortex of iKn mice under basal conditions. In
conclusion, kidneys of iKn mice were protected against ischemic ARF.
This protective effect may be related to a compensatory up-regulation
of heat shock protein 72.
Received 17 December 1998; accepted in final form 19 May 1999.
APS Manuscript Number F328-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 14 June 1999