Alterations in renal hemodynamics are associated with increased renal MMP‐2 expression during the early phase of diabetic nephropathy

Abstract

The aim of the present study was to compare the early changes in proteinuria, renal hemodynamics and matrix metalloproteinase‐2 (MMP‐2, marker of renal injury) expression in type‐1 diabetic SS rats that are susceptible to renal injury versus diabetic Sprague Dawley (SD) rats that are resistant to renal disease. Rats were fed a low salt diet (0.3% NaCl) to minimize the development of hypertension and injected with streptozotocin (STZ, 50 mg/kg, i.p.) to induce diabetes. Blood glucose levels were similar in both strains 3 weeks after diabetes (487±53 mg/dL). Proteinuria increased to 227±19 mg/day in diabetic SS rats while it only increased to 28±5 mg/day in diabetic SD rats. Mean arterial pressure was significantly increased in diabetic SS rats compared to diabetic SD rats (124±4 vs. 106±7 mmHg, respectively). Three weeks of diabetes caused a 2‐fold rise in glomerular filtration rate in both strains; however, renal blood flow was significantly higher in diabetic SS rats compared to values observed in diabetic SD rats. The expression of the active form of MMP‐2 protein was markedly increased in the renal cortex of SS rats compared to SD rats when treated with STZ for 3 weeks. These data suggest that the upregulation in renal MMP‐2 expression may be due to the hyperglycemia‐mediated elevation in hemodynamic stress to the glomeruli leading to the development of severe proteinuria in the SS strain compared to the SD strain.