Renal fibrosis in diabetic and aortic-constricted hypertensive rats

Abstract

To assess if the renal damage observed in rats with diabetes and hypertension is due to hemodynamic or metabolic changes, a progressive aortic constriction between the two renal arteries has been done in streptozotocin-induced diabetic rats (constriction + diabetes group) and in nondiabetic rats (constriction group). This model allows us to study two kidneys subjected to different perfusion pressure (PP) in the same metabolic environment. One-month-old rats (100-120 g body wt) were subjected to the aortic constriction procedure. Three months after constriction, glomerular filtration rate and renal plasma flow were similar in both kidneys of the two groups. PP was greater in the kidney placed over the ligature [constriction high-pressure kidney (CH) or constriction + diabetic high-pressure kidney (DH)] than in the one placed below the ligature [constriction low pressure (CL) or constriction + diabetic low pressure (DL)]. Proteinuria was higher in the CH than in the CL kidneys (512 +/- 61 vs. 361 +/- 38 microg/30 min, respectively) and much higher in the DH kidney (770 +/- 106 microg/30 min). Renal fibrosis was measured in tissue sections stained with Syrius red using a computer-assisted image analysis system. DH and DL kidneys showed higher corpuscular cross-sectional and capillary tuft areas than the CH and CL ones. The DH kidney showed slight mesangial expansion and thickening of the capillary walls, which were more pronounced in the former. Most renal corpuscles from CH and DH groups were nearly normal in morphology appearance, and only in some instances a slight increment in mesangium was observed. Transforming growth factor-beta1 (TGF-beta1) immunostaining revealed that DH kidneys showed the highest glomerular expression. We concluded that 1) diabetic animals develop glomerular but not interstitial fibrosis to a greater extent than nondiabetic animals and that this lesion principally occurs in the hypertensive kidney (DH), and 2) increased TGF-beta expression is associated with diabetic renal damage.

Indapamide Lowers Blood Pressure by Increasing Production of Epoxyeicosatrienoic Acids in the Kidney

“…The role of TGF-b1 in renal fibrosis is widely accepted (Schnaper et al, 2002). Enhanced expression of TGF-b1 has been shown to contribute to the development of renal fibrosis in hypertensive rats (Gallego et al, 2001). The present study revealed that indapamide treatment reduced renal collagen deposition, decreased levels of TGF-b1, and inhibited the activation of p38 and JNK in the renal cortex of SHRs, suggesting that indapamide may reduce renal inflammation and fibrosis by decreasing oxidative stress and MAPK activation.…”

Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats

“…Sections were stained with hematoxylin and eosin for morphological analysis and with Masson’s trichrome to detect fibrosis and then examined by light microscopy. In sections stained with Masson’s trichrome, interstitial fibrosis was measured using computer-assisted image analysis, and the percent fibrosis was calculated [21,22]. The widths of 30 individual cardiomyocytes in each group were measured as previously described.…”

Etiopathology of chronic tubular, glomerular and renovascular nephropathies: Clinical implications

“…As in many other cardiovascular pathological situations, local RAS has been decisively implicated in tissue alteration and remodelling. Renal TGF-β, NF-κB and other cytokines are upregulated in a model of hypercholesterolemic renovascular CKD [229], and also in a model of aortic coarctation between both renal arteries, which pathologically resembles unilateral stenosis [230,231]. They might mediate the inflammatory, fibrotic and apoptotic events, as described generally for glomerular and tubular diseases [208].…”

“…In unilateral stenosis (and associated experimental models, e.g. the Goldblatt experimental model of unilateral stenosis, "two-kidney, one-clip" -2K1C-, and the aortic coarctation between the renal arteries) the non stenotic kidney also undergoes structural alterations [230,231], probably as a consequence of the developed hypertension, or as a result of the systemic or local humoral alterations switched as a compensatory response. In fact, TGF-β expression is upregulated as well in the contralateral kidney by 3-5 weeks after stenosis in 2K1C [235].…”