Key result
The kidneys of OLETF rats with type 2 diabetes showed significantly higher quantitative scores for glomerulosclerosis and interstitial fibrosis, as well as increased nNOS and COX-2 production, compared to control LETO rats.
Supports nNOS/COX-2 role in diabetic renal fibrosis in rats; hypothesis-generating for human therapeutic targeting.
Neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) regulate the tubuloglomerular feedback (TGF) and renin-angiotensin system (RAS) in the kidney. In type 1 diabetic rats, renal overproduction of these enzymes and their relationship to the pathogenesis of diabetic nephropathy has been demonstrated. In the present study, we histologically and immunohistochemically investigated the kidneys of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as a model of type 2 diabetes, at 62 weeks of age (chronic phase of diabetes). The kidneys of OLETF rats showed typical diabetic nephropathy. Quantitative scores for glomerulosclerosis and interstitial fibrosis in OLETF rats were significantly higher than those of age-matched control Long-Evans Tokushima Otsuka (LETO) rats. nNOS- and COX-2-positive immunoreactions were observed in the distal tubules and collecting ducts. These reactions appeared to be more widely distributed in OLETF, and the number of nNOS-and COX-2-positive sites in the OLETF were significantly more than those in LETO rats. Expression of renin, angiotensin II, and inducible nitric oxide synthase (iNOS) were also examined immunohistochemically, and no differences between OLETF and LETO rats were observed in the distributions and the number of immunoreactive-sites. In conclusion, the overproduction of nNOS and COX-2 in the kidney of OLETF rats was confirmed, suggesting that the overproduction of nNOS and/or COX-2 does not affect the intrarenal RAS or iNOS production but does affect TGF.
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Yabuki et al. (2006) studied Diabetic nephropathy (n=10). Type 2 diabetes (OLETF rat model) vs. Control (LETO rats) was evaluated on Quantitative scores for glomerulosclerosis and interstitial fibrosis, and number of nNOS- and COX-2-positive sites. The kidneys of OLETF rats with type 2 diabetes showed significantly higher quantitative scores for glomerulosclerosis and interstitial fibrosis, as well as increased nNOS and COX-2 production, compared to control LETO rats.
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