This Article Full Text Full Text (PDF) 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 Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brink, M. Articles by Delafontaine, P. Search for Related Content PubMed PubMed Citation Articles by Brink, M. Articles by Delafontaine, P.

Angiotensin II Induces Skeletal Muscle Wasting through Enhanced Protein Degradation and Down-Regulates Autocrine Insulin-Like Growth Factor I¹

Division of Cardiology, University Hospital of Geneva (M.B., J.C., A.A., P.D.), CH-1211 Geneva, Switzerland; and Renal Division, Emory University (S.R.P., J.L.B., W.E.M.), Atlanta, Georgia 30322

Address all correspondence and requests for reprints to: Dr. Marijke Brink, Division of Cardiology, Fondation pour Recherches Médicales, 64 avenue de la Roseraie, CH-1211 Geneva, Switzerland. E-mail: marijke.brink{at}dim.hcuge.ch

We previously showed that angiotensin II (ang II) infusion in the rat produces cachexia and decreases circulating insulin-like growth factor I (IGF-I). The weight loss derives from an anorexigenic response and a catabolic effect of ang II. In these experiments we assessed potential catabolic mechanisms and the involvement of the IGF-I system in these responses to ang II. Ang II infusion caused a significant decrease in body weight compared with that of pair-fed control rats. Kidney and left ventricular weights were significantly increased by ang II, whereas fat tissue was unchanged. Skeletal muscle mass was significantly decreased in the ang II-infused rats, and a reduction in lean muscle mass was a major reason for their overall loss of body weight. In skeletal muscles, ang II did not significantly decrease protein synthesis, but overall protein breakdown was accelerated; inhibiting lysosomal and calcium-activated proteases did not reduce the ang II-induced increase in muscle proteolysis. Circulating IGF-I levels were 33% lower in ang II rats vs. control rats, and this difference was reflected in lower IGF-I messenger RNA levels in the liver. Moreover, IGF-I, IGF-binding protein-3, and IGF-binding protein-5 messenger RNAs in the gastrocnemius were significantly reduced. To investigate whether the reduced circulating IGF-I accounts for the loss in muscle mass, we increased circulating IGF-I by coinfusing ang II and IGF-I, but this did not prevent muscle loss. Our data suggest that ang II causes a loss in skeletal muscle mass by enhancing protein degradation probably via its inhibitory effect on the autocrine IGF-I system.

This article has been cited by other articles:

				M. J. Tisdale Mechanisms of Cancer Cachexia Physiol Rev, April 1, 2009; 89(2): 381 - 410. [Abstract] [Full Text] [PDF]

				A. Vigano, B. Trutschnigg, R. D. Kilgour, N. Hamel, L. Hornby, E. Lucar, W. Foulkes, M. L. Tremblay, and J. A. Morais Relationship Between Angiotensin-Converting Enzyme Gene Polymorphism and Body Composition, Functional Performance, and Blood Biomarkers in Advanced Cancer Patients Clin. Cancer Res., April 1, 2009; 15(7): 2442 - 2447. [Abstract] [Full Text] [PDF]

				L. Zhang, J. Du, Z. Hu, G. Han, P. Delafontaine, G. Garcia, and W. E. Mitch IL-6 and Serum Amyloid A Synergy Mediates Angiotensin II-Induced Muscle Wasting J. Am. Soc. Nephrol., March 1, 2009; 20(3): 604 - 612. [Abstract] [Full Text] [PDF]

				S. J. Pocock, J. J.V. McMurray, J. Dobson, S. Yusuf, C. B. Granger, E. L. Michelson, J. Ostergren, M. A. Pfeffer, S. D. Solomon, S. D. Anker, et al. Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme Eur. Heart J., November 1, 2008; 29(21): 2641 - 2650. [Abstract] [Full Text] [PDF]

				A. P. Jayasooriya, M. L. Mathai, L. L. Walker, D. P. Begg, D. A. Denton, D. Cameron-Smith, G. F. Egan, M. J. McKinley, P. D. Rodger, A. J. Sinclair, et al. Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance PNAS, May 6, 2008; 105(18): 6531 - 6536. [Abstract] [Full Text] [PDF]

				P. Costelli, M. Muscaritoli, M. Bossola, F. Penna, P. Reffo, A. Bonetto, S. Busquets, G. Bonelli, F. J. Lopez-Soriano, G. B. Doglietto, et al. IGF-1 is downregulated in experimental cancer cachexia Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R674 - R683. [Abstract] [Full Text] [PDF]

				M. Paul, A. Poyan Mehr, and R. Kreutz Physiology of local Renin-Angiotensin systems. Physiol Rev, July 1, 2006; 86(3): 747 - 803. [Abstract] [Full Text] [PDF]

				G. R. Adams and N. D. Vaziri Skeletal muscle dysfunction in chronic renal failure: effects of exercise Am J Physiol Renal Physiol, April 1, 2006; 290(4): F753 - F761. [Abstract] [Full Text] [PDF]

				P. C. Schulze, J. Fang, K. A. Kassik, J. Gannon, M. Cupesi, C. MacGillivray, R. T. Lee, and N. Rosenthal Transgenic Overexpression of Locally Acting Insulin-Like Growth Factor-1 Inhibits Ubiquitin-Mediated Muscle Atrophy in Chronic Left-Ventricular Dysfunction Circ. Res., September 2, 2005; 97(5): 418 - 426. [Abstract] [Full Text] [PDF]

				V. Roelfsema, A. J. Gunn, B. H. Breier, J. S. Quaedackers, and L. Bennet The Effect of Mild Hypothermia on Insulin-like Growth Factors After Severe Asphyxia in the Preterm Fetal Sheep Reproductive Sciences, May 1, 2005; 12(4): 232 - 237. [Abstract] [PDF]

				A. Cabassi, P. Coghi, P. Govoni, E. Barouhiel, E. Speroni, S. Cavazzini, A. M. Cantoni, R. Scandroglio, and E. Fiaccadori Sympathetic Modulation by Carvedilol and Losartan Reduces Angiotensin II-Mediated Lipolysis in Subcutaneous and Visceral Fat J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2888 - 2897. [Abstract] [Full Text] [PDF]

				N. Ishizaka, K. Saito, E. Noiri, M. Sata, H. Ikeda, A. Ohno, J. Ando, I. Mori, M. Ohno, and R. Nagai Administration of ANG II induces iron deposition and upregulation of TGF-{beta}1 mRNA in the rat liver Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2005; 288(4): R1063 - R1070. [Abstract] [Full Text] [PDF]

				J. P. Porter and K. R. Potratz Effect of intracerebroventricular angiotensin II on body weight and food intake in adult rats Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R422 - R428. [Abstract] [Full Text] [PDF]

				M. R. Rosen The Electrocardiogram 100 Years Later: Electrical Insights Into Molecular Messages Circulation, October 22, 2002; 106(17): 2173 - 2179. [Full Text] [PDF]

				N. Nagaya, M. Uematsu, M. Kojima, Y. Date, M. Nakazato, H. Okumura, H. Hosoda, W. Shimizu, M. Yamagishi, H. Oya, et al. Elevated Circulating Level of Ghrelin in Cachexia Associated With Chronic Heart Failure: Relationships Between Ghrelin and Anabolic/Catabolic Factors Circulation, October 23, 2001; 104(17): 2034 - 2038. [Abstract] [Full Text] [PDF]