L-NAME Administration Enhances Diabetic Kidney Disease Development in an STZ/NAD Rat Model

Figures

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  Figure 1. Changes in body weight (A,B), food consumption (C,D), water intake (E,F), and urinary volume (G,H) in STZ/NAD and STZ/NAD/L-NAME rats for a period of 9 or 12 weeks. Data are presented as mean ± SEM. * p < 0.05 vs. STZ/NAD, # p < 0.05 vs. non-diabetic control animals, and ° p < 0.05 vs. baseline values.

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  Figure 2. Blood glucose levels in diabetic STZ/NAD and STZ/NAD/L-NAME rats for a period of 9 (A) or 12 weeks (B) and non-diabetic control rats. Data are presented as mean ± SEM. * p < 0.05 vs. STZ/NAD, # p < 0.05 vs. non-diabetic control animals, and ° p < 0.05 vs. baseline values.

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  Figure 3. Serum creatinine (A,B), creatinine clearance (C,D), and urinary albumin-to-creatinine ratio (E,F) in STZ/NAD- and STZ/NAD/L-NAME rats for a period of 9 or 12 weeks. Data are presented as mean ± SEM. * p < 0.05 vs. STZ/NAD, ** p < 0.01 vs. STZ/NAD, # p < 0.05 vs. control, and ° p < 0.05 vs. week 0.

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  Figure 4. Systolic (A,B) and diastolic (C,D) blood pressure of STZ/NAD and STZ/NAD/L-NAME diabetic rats for a period of 9 (A,C) or 12 weeks (B,D) and non-diabetic control rats. Data are presented as mean ± SEM. * p < 0.05 vs. STZ/NAD, # p < 0.05 vs. control, and ° p < 0.05 vs. week 0.

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  Figure 5. Histopathology staining of DKD. PAS-stained renal sections of a non-diabetic control rat (A), STZ/NAD (B) and STZ/NAD/L-NAME diabetic rat at week 12 (C). Tubular epithelial cell necrosis (asterisk), tubular atrophy (dashed arrow), thickening of tubular basement membrane (arrow), and tubular dilatation (#). Tubular lesions were quantified in control, STZ/NAD, and STZ/NAD/L-NAME rats after 9 weeks (D) and 12 weeks (E).

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  Figure 6. Semi-quantitative grading of renal interstitial histopathology according to 4 different degrees of severity (A). PAS-stained renal sections of STZ/NAD, STZ/NAD/-L-NAME diabetic rats and non-diabetic control rats were analyzed blinded by a researcher at week 9 (B) and week 12 (C) and divided into the following categories: Degree 1: normal interstitium; degree 2: >70 % normal interstitium; degree 3: >50% normal interstitium; degree 4: <50% normal interstitium. Chi-square analysis was performed. * p < 0.05 vs. STZ/NAD, # p < 0.05 vs. control.

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  Figure 7. Jones methenamine silver-stained renal section of a non-diabetic control rat (A), STZ/NAD (B) and STZ/NAD/L-NAME (C) diabetic rat at week 12. Glomeruli of the diabetic rat show mild mesangial expansion (#) and diffuse thickening of capillary walls (dashed arrow). Tubular lesions manifested as tubular epithelial cell necrosis (asterisk) and tubular atrophy (arrow).

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  Figure 8. Jones methenamine silver-stained renal sections of a control (A), STZ/NAD (B), and STZ/NAD/L-NAME (C) rat after 12 weeks. The glomerulus exhibited hyalinosis of both the afferent and the efferent (arrow) arterioles in the STZ/NAD/L-NAME diabetic rats. Tubular epithelial cell injury (asterisk) was also visible.

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  Figure 9. Study setup. Created with BioRender.