Involvement of angiotensin II in progression of renal injury in rats with genetic non-insulin-dependent diabetes mellitus (Wistar fatty rats)

Wistar fatty (WF) rats have a genetic predisposition to hyperglycemia, poly uria, hyperinsulinemia, hyperlipidemia, obesity and nephropathy. These phen otypic characteristics are similar to those observed in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) nephropathy. In this study , the effects of two types of renin-angiotensin system inhibitors, an angio tensin II type I-receptor antagonist (AT(1)A) and an angiotensin I-converti ng enzyme inhibitor (ACEI), on renal injury in WF rats were studied during the progressive phase of diabetic nephropathy. An AT(1)A, candesartan cilex etil (1 mg/kg), and an ACEI, enalapril (10 mg/kg), were administered orally once a day for 12 weeks, beginning when the rats were 27-week-old and alre ady showed diabetic nephropathy and obesity. Both drugs prevented an increa se in proteinuria during the experimental period. Furthermore, after 4-week intervention, the levels of proteinuria were markedly lower in drug-treate d rats. At the end of the experiment, both drugs prevented the development of glomerular lesions without affecting glucose metabolism and obesity. In conclusion, the inhibition of angiotensin LI activity ameliorated both exis ting proteinuria and the progression of proteinuria, resulting in preservat ion of glomerular structure. Thus angiotensin II plays important roles in t he development and the progression of nephropathy in genetically obese diab etic WF rats.