T. Yoshimoto et al., ANTIHYPERTENSIVE AND VASCULOPROTECTIVE AND RENOPROTECTIVE EFFECTS OF PIOGLITAZONE IN GENETICALLY-OBESE DIABETIC RATS, American journal of physiology: endocrinology and metabolism, 35(6), 1997, pp. 989-996
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.