Chronic nitric oxide deficiency and progression of kidney disease after renal mass reduction in the C57Bl6 mouse.
OBJECTIVE
the C57Bl6 mouse is resistant to chronic kidney disease (CKD) induced by reduction of renal mass (RRM). Nitric oxide (NO) deficiency exacerbates CKD progression so this study investigated whether combination of RRM and NO deficiency would render the C57Bl6 mouse vulnerable to CKD.


METHODS
we used wild-type (WT) mice with RRM, chronic NO synthase (NOS) inhibition and a combination. Also, endothelial NOS (eNOS) knockout (KO) C57Bl6 mice were studied with and without RRM. Primary endpoints were albuminuria and structural damage.


RESULTS
both nonselective (+L-NAME) and neuronal NOS 'selective' (+7NI) NOS inhibition greatly exacerbated the albuminuria and structural damage seen with RRM in the WT mice; NOS inhibition alone had little effect. The eNOS KO mice showed marked structural damage and significant albuminuria in the shams and RRM produced minimal exacerbation of structural damage although the albuminuria was massively amplified.


CONCLUSIONS
these studies demonstrate that the C57Bl6 mouse is rendered vulnerable to RRM-induced CKD when concomitant NO deficiency is produced. This observation supports previous work in CKD-resistant rats and suggests that NO deficiency is required for progression of CKD.
Department of Pulmonology, Semmelweis University, Budapest, Hungary.
Veronika
V
Muller
You-Lin
YL
Tain
Byron
B
Croker
Chris
C
Baylis
D000419:Albuminuria; D000818:Animals; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000378:metabolism*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase