ANTIHYPERTENSIVE AND VASCULOPROTECTIVE AND RENOPROTECTIVE EFFECTS OF PIOGLITAZONE IN GENETICALLY-OBESE DIABETIC RATS

Although an improvement of insulin sensitivity has been shown to be a new therapeutic approach for treating diabetes mellitus, details of ef fects of this treatment on the cardiovascular system and possible rena l complications remain unknown. In the present study, we investigated the effects of a thiazolidine derivative, pioglitazone, and examined t he insulin-sensitizing action on blood pressure, nephropathy, and vasc ular changes in genetically obese diabetic Wistar fatty (WF) rats. Pio glitazone (3 mg.kg(-1).day(-1)) was orally administered for 13 wk star ting at the age of 5 wk, and the results were compared with those of v ehicle-treated WF rats. At the age of 18 wk, vehicle-treated WF rats w ere associated with mild hypertension, nephropathy with proteinuria, h istological glomerular injury, and renal arteriolosclerosis in additio n to hyperglycemia, hyperinsulinemia, and hyperlipidemia. Treatment wi th pioglitazone significantly improved glucose and lipid metabolism. I n addition, it lowered blood pressure, decreased proteinuria, and prev ented glomerular injury, renal arteriolosclerosis, and aortic medial w all thickening, whereas body weight, food intake, sodium balance, and urinary norepinephrine excretion were significantly increased. These r esults suggest that the insulin-sensitizing agent pioglitazone is effe ctive in correcting not only glucose and lipid metabolism but also car diovascular and renal complications in non-insulin-dependent diabetes mellitus.