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1 Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA
2 Department of Pathology, University of California San Francisco, San Francisco, CA, USA
* To whom correspondence should be addressed. E-mail: erdely{at}pitt.edu.
The Wistar Furth (WF) rat is protected against chronic renal disease (CRD) following 5/6th ablation/infarction (A/I) vs the Sprague Dawley (SD) and protection was associated with preserved renal NO production. This study examined CRD induced with repeated administration of puromycin aminonucleoside (PAN). SD PAN developed nephrotic range proteinuria (>1g/24h) and at 15 weeks severe renal injury developed and glomerular filtration rate (GFR) reduced to ~10% of sham. Total NO production, renal NOS activity and renal neuronal (n) and medullary endothelial (e) NOS abundance was reduced in the SD PAN. WF PAN exhibited less severe initial proteinuria (>400mg/24h) which abated within weeks while GFR was normal and injury was minimal at 15 weeks. Total NO production and renal NOS activity and abundance was significantly elevated compared to SD PAN. NOS mRNA (nNOS, eNOS and inducible (i)NOS) was not altered in WF while SD showed significant increases in NOS gene expression with PAN. In conclusion, WF show resistance to a second model of CRD with maintained renal NOS activity compared to SD.
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