Key result
5/6 nephrectomy induces CKD in Sprague-Dawley but not Wistar rats, driven by intrarenal nitric oxide differences.
Why the study?
Understanding the mechanisms conditioning development of chronic kidney disease remains a challenge, particularly the role of the intrarenal nitric oxide pathway in sensitivity or resistance to CKD.
In a 5/6 nephrectomy model, Sprague-Dawley rats are sensitive and Wistar rats are resistant to developing chronic kidney disease, a difference potentially mediated by variations in intrarenal nitric oxide pathway activity.
Strain-specific intrarenal NOS differences may explain variable CKD susceptibility in 5/6 nephrectomy; leaves open human translational relevance.
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.
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Saracyn et al. (2017) studied Chronic kidney disease. 5/6 nephrectomy vs. Wistar vs Sprague-Dawley strains was evaluated on Parameters of renal failure and expression of nitric oxide synthase (NOS) isoforms in renal cortex and medulla. 5/6 nephrectomy induced chronic kidney disease in Sprague-Dawley rats but not in Wistar rats, with differences in intrarenal nitric oxide pathway activity differentiating the strains' sensitivity.
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