Evidence for the Existence of Two Distinct Functions for the Inducible NO Synthase in the Rat Kidney

Abstract

Abstract. The functional role of the NO synthase (NOS) isoforms in the normal or diseased kidney is uncertain. This study examined the renal expression of the endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) isoforms by both immunohistochemistry and Western blot analyses in shamoperated rats (S) and in rats subjected to 5/6 nephrectomy (Nx). Primary antibodies from two different sources were used to detect iNOS. Additional S and Nx rats were chronically treated with aminoguanidine (AG), a selective iNOS inhibitor. All three isoforms were clearly expressed in S kidney. Their renal abundance, evaluated by Western blot analysis, fell in Nx rats. With the use of anti-iNOS antibodies from two distinct sources, the immunohistochemical analysis showed the presence of what appeared to be two distinct iNOS fractions: a "tubular" fraction, present in S and with decreased intensity in Nx; and an "interstitial" fraction, observed only in inflamed areas of Nx rats. AG treatment greatly attenuated renal injury in Nx rats by a direct antiinflammatory effect, likely related to iNOS inhibition, rather than to amelioration of renal hemodynamics or to reduced protein glycation. These observations suggest that: (1) the functional role of the renal iNOS isoform may vary dramatically under different physiologic conditions; (2) caution should be taken in the interpretation of immunohistochemical iNOS data, because antibodies from different sources may detect different iNOS fractions; and (3) AG treatment may become useful in the treatment of human progressive nephropathies, even those not associated with diabetes or aging.

Protection of Wistar Furth Rats from Chronic Renal Disease Is Associated with Maintained Renal Nitric Oxide Synthase

“…The protein abundance of eNOS seems to be variable in models of renal mass reduction associated with significant injury, and in- creases (20), decreases (15,18,19), and no change (1) (this study) have been reported. The reasons for these differences are unclear but may be related to differences in rat strain, extent of renal mass reduction, time after renal mass reduction, or ablation versus A/I treatment.…”

“…Studies using renal mass reduction have also demonstrated decreased nNOS, inducible NOS, and eNOS levels in the remnant kidney (15,16,18,19). Our laboratory recently demonstrated that renal nNOS levels were consistently reduced in several models of CRD in SD rats.…”

Effects of a selection of histone deacetylase inhibitors on mast cell activation and airway and colonic smooth muscle contraction

“…These disparate findings are not completely incompatible, since iNOS in one and same organ or tissue may exist in distinct fractions, e.g. in the kidney where interstitial iNOS differs from tubular iNOS in the inhibition by aminoguanidine [37]. An added complication is that the expression of iNOS gene, like other genes induced in inflammatory responses, may vary according to the cell type and the stimulus, and thus may be upregulated [20] or downregulated [38] by HDAC inhibitors.…”

Dietary L-Arginine Supplementation Improves the Glomerular Filtration Rate and Renal Blood Flow After 24 Hours of Unilateral Ureteral Obstruction in Rats

“…However, it was recently shown that completely different staining patterns were found using 2 different, commercially available anti-iNOS antibodies. 17 In addition, iNOS expressions was increased in the CK. Compensatory changes in the CK in UUO have been reported, 18 and the up-regulation of NOS and subsequent NO production may be involved in these changes.…”