Down-regulation of nitric oxide synthase in the diabetic rabbit kidney: potential relevance to the early pathogenesis of diabetic nephropathy

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Abstract
SUMMARYObjectives: Nephropathy is a well-recognised complication of diabetes mellitus (DM). The aim of this study was to investigate the effect of DM on the density and distribution of nitric oxide (NO) synthase (NOS) in the rabbit kidney. Quantification of the NOS radioligand on slide-mounted sections was compared with the nitroblue tetrazolium reaction, where the intensity of the reaction varies with the nicotinamide adenine dinucleotide diaphorase (NADPH-d) activity of NOS.Materials and methods: DM was induced with alloxan in six New Zealand White (NZW) rabbits. Plasma creatinine, urea and electrolytes were monitored at monthly intervals. The kidneys were removed following 6 months of DM. Transverse serial sections were cut and low-resolution autoradiography was performed using a radioligand for NOS ([3H]-NOARG). Histochemical localisation of NADPH-d activity was also performed. Densitometric analysis was performed on the autoradiographs and the results compared with those obtained from six age-matched...