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(Hypertension. 2001;38:1255.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Candesartan Inhibits Carotid Intimal Thickening and Ameliorates Insulin Resistance in Balloon-Injured Diabetic Rats

Masahiko Igarashi; Akihiko Hirata; Hiroshi Yamaguchi; Hiromi Tsuchiya; Hiroshi Ohnuma; Makoto Tominaga; Makoto Daimon; Takeo Kato

Third Department of Internal Medicine (M.I., H.Y., H.T., H.O., M.D., T.K.) and the Department of Laboratory Medicine (A.H., M.T.), Yamagata University School of Medicine, Yamagata, Japan.

Correspondence to Masahiko Igarashi, MD, Third Department of Internal Medicine, Yamagata University School of Medicine, 2-2-2, Iida-nishi, Yamagata 990-9585, Japan. E-mail migarasi{at}med.id.yamagata-u.ac.jp

This study investigates the effects of candesartan, an angiotensin II type 1 receptor blockade, on carotid arterial intimal thickening and glucose tolerance in balloon-injured male Wistar fatty rats and their littermates (Wistar lean rats). Candesartan was orally administered to 12-week-old rats for 21 days, and age-matched rats without the agent were used as the respective controls. Balloon catheterization in the left common carotid artery was performed on day 7, and the artery was removed on day 14 for histological analysis. Compared with the area ratios of the neointima/media in fatty rats without treatment, the ratios in fatty rats treated with candesartan at 1 mg · kg^-1 · d^-1 and lean rats without treatment were significantly decreased to 65%; on the other hand, the ratios of fatty rats treated with candesartan at 10 mg · kg^-1 · d^-1 and lean rats treated with 1 mg · kg^-1 · d^-1 were reduced to 35%, and those of lean rats treated with 10 mg · kg^-1 · d^-1 were reduced to 28%. The administration of candesartan also decreased the level of plasma glucose time- and dose-dependently in fatty rats. In an intragastric glucose load, the levels of both glucose and insulin at 30 and 60 minutes were significantly decreased when fatty rats were treated with candesartan at 10 mg · kg^-1 · d^-1. In cultured vascular smooth muscle cells from fatty rats, insulin-stimulated Akt (New England Biolabs) phosphorylation and 2-deoxy-D-glucose uptake were inhibited to 59% and 68%, respectively, by angiotensin II, but the effects were ameliorated by the addition of 10^-7 mol/L candesartan. We conclude that candesartan could be effective for the suppression of vascular smooth muscle cell growth dose-dependently in Wistar fatty and lean rats. Furthermore, the agent could improve insulin resistance in Wistar fatty rats.

Key Words: angiotensin II • receptors, angiotensin II • rats • balloon injury • insulin resistance

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