Rapid development of glomerulosclerosis in diabetic Dahl salt-sensitive rats

Abstract

Summary Diabetic nephropathy tends to develop more readily in patients with a family history of hypertension and/or disturbances in sodium transport across the plasma membrane. This prompted us to study the renal effects of diabetes mellitus in a rat strain which is predisposed to develop salt-sensitive hypertension, the Dahl salt-sensitive rat. Diabetes is associated with several aberrations in the renal handling of sodium, such as elevation of tubular Na + , K + ATPase activity. This effect was more pronounced in Dahl salt-sensitive than in Dahl salt-resistant rats. Severe renal lesions, characteristic of the advanced phase of diabetic nephropathy are very rarely observed in rats with streptozotocin diabetes. However, 2 months after induction of diabetes, the Dahl salt-sensitive rats had morphological signs of advanced glomerular disease. The urinary albumin concentration was very high, but did not correlate with the blood pressure. Non-diabetic Dahl salt-sensitive rats as well as Dahl salt-resistant diabetic and non-diabetic rats had little or no signs of glomerular disease and consistently very low urinary albumin concentrations. [Diabetologia (1997) 40: 367-373]

Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats.

“…The dopamine 1 receptor antagonist, SCH 23390, was given as an intravenous infusion at 30 µg · kg body wt -1 · h -1 . Because we previously showed that glomerulosclerosis progresses rapidly in Dahl salt-sensitive diabetic rats (21), the effect of nitecapone on manifestations of diabetic nephropathy (albuminuria and renal morphology) was studied using this rat model. All other studies were performed with Sprague-Dawley rats.…”

“…Renal function. In Sprague-Dawley rats (n = 5) diabetic for 10 days, glomerular filtration rate (GFR) was measured as the clearance of inulin, as previously described (21). Briefly, a 5% solution of Inutest (Laevosan; Gesellschaft, Linz, Austria) diluted in Ringer's solution was infused at a dose of 1% of body wt/h.…”

“…Measurement of Na,KATPase activity was performed in Sprague-Dawley rats (n = 6) 10 days after the induction of diabetes. Kidney perfusion and tubule dissection were performed as previously described (21). Briefly, the left kidney was perfused with a cold modified Hanks' buffer solution containing (in mmol/l): 137 NaCl, 5 KCl, 0.8 MgSO 4 , 0.33 Na 2 HPO 4 , 0.44 KH 2 PO 4 , 1 CaCl 2 , 1 MgCl 2 , 10 Tris-HCl (pH 7.4), 0.05% collagenase (Sigma), and 0.1% bovine serum albumin (BSA) (Behringwerke, Marburg, Germany).…”

“…Renal morphology. Morphometric analysis was performed 8 weeks after the induction of diabetes in Dahl salt-sensitive rats (n = 6-8), as previously described (21). In brief, the left kidney was immersion fixed in 4% paraformaldehyde, embedded in paraffin, and cut into 3 coronal blocks that were each 1.5 mm thick.…”

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

“…To assess the contribution of hypertension to diabetic renal disease, studies were performed in different animal models, including diabetic hypertensive Dahl salt-sensitive rats, 15 Goldblatt hypertension, wherein one renal artery is constricted and the contralateral kidney is left intact with streptozotocin-induced diabetes, 16 and spontaneously hypertensive/National Institute of Health (NIH)-corpulent rats, which are a model of type 2 diabetic nephropathy. 17 However, most of these studies were performed in a genetic model of hypertension, namely a spontaneously hypertensive rat (SHR) that was rendered diabetic by injection of streptozotocin.…”