Nitric oxide prevents neutrophil mediated acute renal failure.
Linas, Stuart, Dennis Whittenburg, John E. Repine.
Department of Medicine, Denver General Hospital, 777 Bannock
Street, Denver, CO 80204
APStracts 3:0171F, 1996.
The contribution of Nitric Oxide (NO) to ischemic acute renal failure
is unclear. Because neutrophils (PMN) accentuate injury in kidneys
subjected to ischemia/reperfusion and because NO has potent vascular
and PMN effects, we examined the contribution of NO to PMN-mediated
injury in isolated perfused rat kidneys. Non-ischemic and ischemic
kidneys were perfused by the isolated kidney technique in the
presence or absence of PMN and NO agonists [sodium nitroprusside
(SNP), L-arginine (L-ARG)] or an NO synthase (NOS) inhibitor [N-w
-nitro-L-arginine (L-NNA)]. In non-ischemic kidneys, the NOS
antagonist decreased perfusion flow rate by 25% without affecting
glomerular filtration rate (GFR) or tubular sodium reabsorption (TNA)
while NOS agonist treatment had no effects. Following 20 min of
ischemia/60 min reperfusion in the absence of PMN, NO agonist
treatment potentiated ischemia/reperfusion-induced loss of GFR and
TNA while adding the NO antagonist lessened glomerular and tubular
injury. Reperfusion of ischemic kidneys with PMN resulted in PMN
retention and potentiated ischemic injury. However, increases in PMN
retention as well as decreases in GFR and TNA caused by PMN were
prevented by SNP and worsened by L-NNA. Moreover, in non-ischemic
kidneys, activated PMN caused renal injury and PMN retention which
were prevented by SNP and worsened by L-NNA. In conclusion, 1) NO
worsens ischemic injury in the absence of PMN; 2) NO prevents the PMN
component of ischemic renal injury by blocking PMN retention and the
deleterious effects of activated PMN on glomerular and tubular
function.
Received 14 December 1995; accepted in final form 20 September
1996.
APS Manuscript Number F415-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996