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Horm Metab Res 2004; 36(7): 458-464
DOI: 10.1055/s-2004-825725
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Possible Role of VEGF in the Progression of Kidney Disease in Streptozotocin (STZ)-induced Diabetic Rats: Effects of an ACE Inhibitor and an Angiotensin II Receptor Antagonist

H.  Kakizawa1, 2 , Y.  Itoh1 , S.  Imamura1 , T.  Matsumoto1 , Y.  Ishiwata1 , Y.  Ono1 , K.  Yamamoto1 , T.  Kato1 , N.  Hayakawa1 , N.  Oda1 , Y.  Goto2 , Y.  Goto2 , A.  Nagasaka1 , T.  Senda3 , M.  Itoh1
  • 1Division of Endocrinology & Metabolism, Department of Internal Medicine, Fujita Health University, School of Medicine, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan
  • 2Department of Internal Medicine, Enshu General Hospital, 144-6, Tokiwa-cho, Hamamatsu, Shizuoka, 430-0917, Japan
  • 3Department of Anatomy I, Fujita Health University, School of Medicine, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan
Further Information

Publication History

Received 1 April 2003

Acceped after second Revision 6 January 2004

Publication Date:
23 July 2004 (online)

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Abstract

Two endothelium-derived factors, endothelin (ET), a vasoconstrictor, and vascular endothelial growth factor (VEGF), an angiogenic factor are thought to be involved in the pathogenesis of diabetic vascular complications. The aim of this study was to determine the effects of an angiotensin II type I (AT-1) receptor antagonist and an ACE inhibitor on the pathogenesis of VEGF and ET-1-mediated kidney disease in STZ-induced diabetic rats. Two days after STZ administration, diabetic rats were treated for 8 weeks with enalapril maleate, an ACE inhibitor, candesartan cilexetil, an AT-1 receptor antagonist, or saline. Urinary albumin and N-acetyl β-D glucosaminidase (NAG) excretion as well as the VEGF protein content in the kidney were all found to be elevated in diabetic rats. Administration of enalapril maleate or candesartan cilexetil decreased the level of microalbuminuria and NAG excretion in diabetic rats. Administration of enalapril maleate also suppressed the elevated renal VEGF protein content in these animals while candesartan cilexetil treatment had no effect. Serum ET-1 and VEGF levels were unchanged by these treatments. These data support a role for AT-1 receptor antagonists and ACE inhibitors in the prevention of diabetic nephropathy, and suggest that the former may work by reducing renal VEGF levels.

Key words

AT-1 - ACE-I - VEGF - Endothelin-1 - Diabetes - Rat

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Prof. M. Itoh, M. D.

The Division of Endocrinology & Metabolism · The Department of Internal Medicine · Fujita Health University · School of Medicine

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