This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Uehara, Y. Articles by Omata, M. Search for Related Content PubMed Articles by Uehara, Y. Articles by Omata, M. Social Bookmarking                         What's this?

Angiotensin-Converting Enzyme Inhibition Delays Onset of Glucosuria With Regression of Renal Injuries in Genetic Rat Model of Non-Insulin-Dependent Diabetes Mellitus

Second Department of Medicine, University of Tokyo, Tokyo, Japan

Nobuhito Hirawa

Department of Nephrology, Kantou-Teishin Hospital, Tokyo, Japan

Atsushi Numabe

Division of Hypertension and Cardiorenal Disease, Department of Medicine, Dokkyo University School of Medicine, Tochigi, Japan

Yukari Kawabata

Second Department of Medicine, University of Tokyo, Tokyo, Japan

Hiroshi Nagoshi

Second Department of Medicine, University of Tokyo, Tokyo, Japan

Hideyuki Negoro

Second Department of Medicine, University of Tokyo, Tokyo, Japan

Satoshi Fujiwara

Second Department of Medicine, University of Tokyo, Tokyo, Japan

Tomoko Gomi

Department of Nephrology, Kantou-Teishin Hospital, Tokyo, Japan

Toshio Ikeda

Department of Nephrology, Kantou-Teishin Hospital, Tokyo, Japan

Atsuo Goto

Second Department of Medicine, University of Tokyo, Tokyo, Japan

Masao Omata

Second Department of Medicine, University of Tokyo, Tokyo, Japan

Background: The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new genetic model of non-insulin-dependent diabetes mellitus (NIDDM). We investigated whether angiotensin inhibition influences the onset of NIDDM and brings about a regression of renal injury in diabetes mellitus.

Methods and Results: Six-week-old OLETF rats were treated with the angiotensin-con verting enzyme (ACE) inhibitors imidapril or enalapril for 16 weeks. Systolic blood pres sure is increased in an age-dependent manner in OLETF rats. In this study, the elevation in systolic blood pressure was dose-dependently reduced by ACE inhibitor treatment. In OLETF rats, plasma concentrations of insulin and glucose increased and the glucosuria occurred at the age of 22 weeks. Simultaneously, OLETF rats exhibited proteinuria and nodular lesions in glomeruli. The ACE inhibitor treatment almost completely reduced glu cosuria, and also decreased plasma concentrations of insulin and glucose in OLETF rats. ACE inhibitor treatment lessened the proteinuria and attenuated morphologically the severity of nodular lesions in OLETF rats. Moreover, increases in plasminogen activator inhibitor 1 (PAI-1) in OLETF rats were reduced by the ACE inhibitor treatment, and the improvement of glomerular lesions was related to decreases of PAI-1 and angiotensin II levels in plasma but not to improvement of glucose metabolism.

Conclusions: ACE inhibitors delay onset of NIDDM with attenuation of kidney injury. The regression of kidney lesions is probably due to angiotensin reduction but not to glucose metabolism per se. ACE inhibitor drug therapy may be useful in preventing NIDDM and the subsequent renal injury in patients with NIDDM.

Key Words: angiotensin-converting enzyme inhibitor • non-insulin-dependent diabetes mel litus • kidney injury • plasminogen activator inhibitor 1.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 3, No. 4, 327-335 (1998)
DOI: 10.1177/107424849800300408


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Lau, I. Sudbury, M. Thomson, P. L. Howard, A. B. Magil, and W. A. Cupples Salt-resistant blood pressure and salt-sensitive renal autoregulation in chronic streptozotocin diabetes Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2009; 296(6): R1761 - R1770. [Abstract] [Full Text] [PDF]

				S. Hashimoto, K. Yamada, T. Kawata, T. Mochizuki, J. Schnermann, and T. Koike Abnormal autoregulation and tubuloglomerular feedback in prediabetic and diabetic OLETF rats Am J Physiol Renal Physiol, March 1, 2009; 296(3): F598 - F604. [Abstract] [Full Text] [PDF]