Anti-hypertensive, vasculo- and reno-protective effects of
pioglitazone in genetically obese-diabetic rat.
Yoshimoto, Takanobu, Mitsuhide Naruse, Megumi Nishikawa, Kiyoko
Naruse, Akiyo Tanabe, Toshirou Seki, Toshihiro Imaki, Reiko Demura,
Eizo Aikawa, and Hiroshi Demura.
Department of Medicine, Institute of Clinical Endocrinology,
Department of Anatomy and Developmental Biology, Tokyo Women's
Medical College, Tokyo 162, Japan
APStracts 4:0026E, 1997.
Although an improvement of insulin sensitivity has been shown to be a
new therapeutic approach for treating diabetes mellitus, details of
effects of this treatment on the cardiovascular system and possible
renal complications remain unknown. In the present study, we
investigated the effects of a thiazolidine derivative, pioglitazone,
examining the insulin sensitizing action on blood pressure,
nephropathy, and vascular changes in genetically obese-diabetic
Wistar fatty (WF) rats. Pioglitazone (3 mg/kg/d) was orally
administered for 13 weeks starting at the age of 5 weeks and the
results were compared with those of vehicle-treated WF rats. At the
age of 18 weeks, vehicle-treated WF rats were associated with mild
hypertension, nephropathy with proteinuria, histological glomerular
injury, and renal arteriolosclerosis in addition to hyperglycemia,
hyperinsulinemia, and hyperlipidemia. Treatment with pioglitazone
significantly improved glucose and lipid metabolism. In addition, it
lowered blood pressure, decreased proteinuria, and prevented the
glomerular injury, renal arteriolosclerosis, and aortic medial wall
thickening, whereas body weight, food intake, sodium balance, and
urinary norepinephrine excretion were significantly increased. These
results suggest that the insulin-sensitizing agent pioglitazone is
effective in correcting not only glucose and lipid metabolism but
also cardiovascular and renal complications in non-insulin-dependent
diabetes mellitus.
Received 19 August 1996; accepted in final form 10 January 1997.
APS Manuscript Number E409-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 19 February 1997