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Updated: Jun 2, 2026
5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
Published on: July 3, 2013
Reciprocal changes of renal neuronal nitric oxide synthase-α and -β associated with renal progression in a neonatal
You-Lin Tain1, Sid Ghosh, Richard J Krieg
1Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University, College of Medicine, Taiwan. tainyl@hotmail.com
Background:
Nitric oxide (NO) deficiency contributes to chronic kidney disease progression. NO deficiency could occur for many reasons, one of which is decreased NO synthase (NOS) abundance and/or activity.
Methods:
In these experiments, we studied two groups of male Sprague Dawley rats given sham or surgical excision of both poles of the left kidney (at 2 days of age) followed by sham or surgical removal of the right kidney at 10 days. Rats were sacrificed at 9 weeks of age and the kidneys examined for abundance of neuronal NOS (nNOS)-α and -β, endothelial NOS, arginase II, argininosuccinate synthase and lysate, protein arginine methyltransferase 1, dimethylarginine dimethylamino-hydrolase 1 and 2, as well as renal pathology.
Results:
The 5/6 nephrectomy (NX) group showed renal dysfunction, severe rapidly progressing glomerulosclerosis, and hypertension. Renal cortical nNOSα abundance was significantly reduced, whereas nNOSβ abundance was increased in the 5/6 NX group versus sham. Renal endothelial NOS was unchanged. Next, renal protein arginine methyltransferase 1 abundance was higher, whereas dimethylarginine dimethylamino-hydrolase 2 expression was lower in the 5/6 NX group versus sham. Renal arginase II, argininosuccinate synthase, and argininosuccinate lysate abundances were significantly decreased in 5/6 NX rats than those in sham.
Conclusion:
The neonatal kidney is very susceptible to 5/6 NX-induced injury, and, as in adults, reciprocal changes in the nNOSα and nNOSβ in renal cortex occur during progression of chronic kidney disease and may contribute to the injury.
