This Article Full Text 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 Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, S. Articles by Iwao, H. Search for Related Content PubMed PubMed Citation Articles by Kim, S. Articles by Iwao, H.

(Hypertension. 1997;30:1054-1061.)
© 1997 American Heart Association, Inc.

Articles

Angiotensin Blockade Improves Cardiac and Renal Complications of Type II Diabetic Rats

Shokei Kim; Hideki Wanibuchi; Akinori Hamaguchi; Katsuyuki Miura; Shinya Yamanaka; Hiroshi Iwao

From the Department of Pharmacology (S.K., A.H., K.M., S.Y., H.I.) and the First Department of Pathology (H.W.), Osaka City University Medical School, Osaka, Japan.

Correspondence to Shokei Kim, MD, Department of Pharmacology, Osaka City University Medical School, 1-4-54 Asahimachi, Abeno, Osaka 545, Japan.

Abstract Using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new model of human non–insulin-dependent diabetes mellitus (NIDDM), we examined the role of local angiotensin II in cardiovascular and renal complications of NIDDM. OLETF rats were orally given cilazapril (an angiotensin-converting enzyme inhibitor, 1 or 10 mg/kg), E4177 (an angiotensin AT₁ receptor antagonist, 10 mg/kg), or vehicle for 26 or 40 weeks (from the age of 20 to 46 or 60 weeks). Cardiac mRNAs were measured by Northern blot analysis, and the thickening of the coronary arterial wall and the degree of perivascular fibrosis were determined by an image analyzer. Cilazapril or E4177 did not significantly affect body weight or plasma glucose and insulin levels of OLETF rats, indicating the minor effects on diabetes itself. However, both drugs significantly and similarly prevented coronary microvascular remodeling (the increase in wall thickening and perivascular fibrosis in coronary arterioles and small coronary arteries) in OLETF rats, and they were associated with the suppression of cardiac transforming growth factor-ß1 expression. Both drugs suppressed not only the increase in left ventricular weight but also the downregulation of cardiac -myosin heavy chain expression in OLETF rats. Glomerulosclerosis and glomerular hypertrophy in OLETF rats were improved by cilazapril and E4177 to a comparable extent. These results, taken together with the fact that OLETF rats show normal plasma renin levels, support that the AT₁ receptor is involved in the pathogenesis of cardiac and renal complications in NIDDM.

Key Words: diabetes mellitus • diabetic nephropathy • angiotensin-converting enzyme inhibition • receptors, angiotensin II • insulin resistance • transforming growth factor

This article has been cited by other articles:

				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]

				S. Kim-Mitsuyama, E. Yamamoto, T. Tanaka, Y. Zhan, Y. Izumi, Y. Izumiya, T. Ioroi, H. Wanibuchi, and H. Iwao Critical Role of Angiotensin II in Excess Salt-Induced Brain Oxidative Stress of Stroke-Prone Spontaneously Hypertensive Rats Stroke, May 1, 2005; 36(5): 1077 - 1082. [Abstract] [Full Text] [PDF]

				R. B. Wichi, S. B. Souza, D. E. Casarini, M. Morris, M. L. Barreto-Chaves, and M. C. Irigoyen Increased blood pressure in the offspring of diabetic mothers Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2005; 288(5): R1129 - R1133. [Abstract] [Full Text] [PDF]

				K. F. Hilgers and R. Veelken Type 2 Diabetic Nephropathy: Never too Early to Treat? J. Am. Soc. Nephrol., March 1, 2005; 16(3): 574 - 575. [Full Text] [PDF]

				S. Jesmin, Y. Hattori, I. Sakuma, C. N. Mowa, and A. Kitabatake Role of ANG II in coronary capillary angiogenesis at the insulin-resistant stage of a NIDDM rat model Am J Physiol Heart Circ Physiol, October 1, 2002; 283 (4): H1387 - H1397. [Abstract] [Full Text] [PDF]

				S. Kim and H. Iwao Molecular and Cellular Mechanisms of Angiotensin II-Mediated Cardiovascular and Renal Diseases Pharmacol. Rev., March 1, 2000; 52(1): 11 - 34. [Abstract] [Full Text] [PDF]

				A. Hamaguchi, S. Kim, Y. Izumi, Y. Zhan, S. Yamanaka, and H. Iwao Contribution of Extracellular Signal-Regulated Kinase to Angiotensin II–Induced Transforming Growth Factor-{beta}1 Expression in Vascular Smooth Muscle Cells Hypertension, July 1, 1999; 34(1): 126 - 131. [Abstract] [Full Text] [PDF]

				S. Kim, Y. Izumi, M. Yano, A. Hamaguchi, K. Miura, S. Yamanaka, H. Miyazaki, and H. Iwao Angiotensin Blockade Inhibits Activation of Mitogen-Activated Protein Kinases in Rat Balloon-Injured Artery Circulation, May 5, 1998; 97(17): 1731 - 1737. [Abstract] [Full Text] [PDF]