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11 October 2017 : Animal Research  

Role of Nitric Oxide Pathway in Development and Progression of Chronic Kidney Disease in Rats Sensitive and Resistant to its Occurrence in an Experimental Model of 5/6 Nephrectomy

Marek Saracyn12ABCDEFG*, Katarzyna Czarzasta3BDE, Marek Brytan4ACE, Piotr Murawski5CD, Sławomir Lewicki6CEF, Tomasz Ząbkowski7BEF, Robert Zdanowski6CDE, Agnieszka Cudnoch-Jędrzejewska2ACD, Grzegorz Wiktor Kamiński1ADG, Zofia Wańkowicz2ACDE

DOI: 10.12659/MSM.903820

Med Sci Monit 2017; 23:4865-4873

Abstract

BACKGROUND: Understanding the mechanisms conditioning development of chronic kidney disease (CKD) is still a challenge. The aim of this study was to evaluate the activity of the intrarenal nitric oxide (NO) pathway in the context of sensitivity or resistance of different animal strains to the development and degree of renal failure.

MATERIAL AND METHODS: Two rat strains were used: Wistar (WR) and Sprague-Dawley rats (SDR) in a model of CKD – 5/6 nephrectomy. We assessed parameters of renal failure and expression of nitric oxide synthase (NOS) isoforms in renal cortex and medulla.

RESULTS: We did not observe renal failure in WR, and CKD developed in SDR with increase of creatinine and urea concentration as well as decrease of diuresis and glomerular filtration. In the renal cortex, baseline expression of NOS2 was higher in WR than in SDR. 5/6 nephrectomy resulted in reduction of NOS2 in both strains and NOS3 in WR. In the renal medulla, baseline NOS2 expression was higher in SDR, and nephrectomy resulted in its decrease only in SDR. Although baseline NOS3 expression was higher in SDR, the NOS3 expression after nephrectomy was higher in WR rats.

CONCLUSIONS: In model of CKD – 5/6 nephrectomy, SDR proved to be sensitive and WR resistant to development of CKD. The intrarenal activity of the nitric oxide pathway was the factor that differentiated both strains. This mechanism may be responsible for insensitivity of WR to development of renal failure in this model of CKD.

Keywords: Models, Animal, Nitric Oxide, Rats, Wistar, Renal Insufficiency, Chronic

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750