Circulation Research, Vol 62, 749-756, Copyright © 1988 by American Heart Association

ARTICLES

Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells

AA Geisterfer, MJ Peach and GK Owens
Department of Physiology, University of Virginia, School of Medicine, Charlottesville.

We have explored the hypothesis that contractile agonists are important regulators of smooth muscle cell growth by examining the effects of one potent contractile agonist, angiotensin II (AII), on both cell proliferation and cellular hypertrophy. AII neither stimulated proliferation of cells made quiescent in a defined serum-free media nor augmented cell proliferation induced by serum or platelet-derived growth factor. However, AII did induce cellular hypertrophy of postconfluent quiescent cultures following 4 days of treatment, increasing smooth muscle cell protein content by 20% as compared with vehicle-treated controls. AII-induced hypertrophy was maximal at 1 microM, had an ED50 of 5 nM, and was blocked by the specific AII receptor antagonist Sar1,Ile8 AII. The cellular hypertrophy was due to an increase in protein synthesis, which was elevated within 6-9 hours following AII treatment, while no changes in protein degradation were apparent. AII was even more effective in inducing hypertrophy of subconfluent cultures, causing a 38% increase in protein content after 4 days of treatment (1 microM) and showing a maximal response at concentrations as low as 0.1 nM. Interestingly, in subconfluent cultures, AII treatment (1 microM, 4 days) was associated with a 50% increase in the fraction of cells with 4C DNA content with the virtual absence of cells in S-phase of the cell cycle, consistent with either arrest of cells in the G2 phase of the cell cycle or development of tetraploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

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				Y Hojo, U Ikeda, T Katsuki, O Mizuno, H Fujikawa, and K Shimada Inhibition of angiotensin converting enzyme cannot prevent increases in angiotensin II production in coronary circulation Heart, May 1, 2000; 83(5): 574 - 576. [Abstract] [Full Text]

				H. Tang, T. Nishishita, T. Fitzgerald, E. J. Landon, and T. Inagami Inhibition of AT1 Receptor Internalization by Concanavalin A Blocks Angiotensin II-induced ERK Activation in Vascular Smooth Muscle Cells. INVOLVEMENT OF EPIDERMAL GROWTH FACTOR RECEPTOR PROTEOLYSIS BUT NOT AT1 RECEPTOR INTERNALIZATION J. Biol. Chem., April 28, 2000; 275(18): 13420 - 13426. [Abstract] [Full Text] [PDF]

				J. Haendeler, M. Ishida, L. Hunyady, and B. C. Berk The Third Cytoplasmic Loop of the Angiotensin II Type 1 Receptor Exerts Differential Effects on Extracellular Signal-Regulated Kinase (ERK1/ERK2) and Apoptosis via Ras- and Rap1-Dependent Pathways Circ. Res., April 14, 2000; 86(7): 729 - 736. [Abstract] [Full Text] [PDF]

				N. K. Hollenberg Hypertension, Small Arteries, and Pathways for Angiotensin II Generation : "The Proper Study of Mankind is Man" Circulation, April 11, 2000; 101(14): 1641 - 1642. [Full Text] [PDF]

				E. L. Schiffrin, J. B. Park, H. D. Intengan, and R. M. Touyz Correction of Arterial Structure and Endothelial Dysfunction in Human Essential Hypertension by the Angiotensin Receptor Antagonist Losartan Circulation, April 11, 2000; 101(14): 1653 - 1659. [Abstract] [Full Text] [PDF]

				A. W. van Gorp, D. S. V. I. Schenau, A. P. G. Hoeks, H. A. J. S. Boudier, J. G. R. de Mey, and R. S. Reneman In spontaneously hypertensive rats alterations in aortic wall properties precede development of hypertension Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1241 - H1247. [Abstract] [Full Text] [PDF]

				K. K. Griendling, D. Sorescu, and M. Ushio-Fukai NAD(P)H Oxidase : Role in Cardiovascular Biology and Disease Circ. Res., March 17, 2000; 86(5): 494 - 501. [Abstract] [Full Text] [PDF]

				D. Lang, S. I. Mosfer, A. Shakesby, F. Donaldson, and M. J. Lewis Coronary Microvascular Endothelial Cell Redox State in Left Ventricular Hypertrophy : The Role of Angiotensin II Circ. Res., March 3, 2000; 86(4): 463 - 469. [Abstract] [Full Text] [PDF]

				Jeong Bae Park, H. D Intengan, and E. L Schiffrin Reduction of resistance artery stiffness by treatment with the AT1-receptor antagonist losartan in essential hypertension Journal of Renin-Angiotensin-Aldosterone System, March 1, 2000; 1(1): 40 - 45. [Abstract] [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]

				M. J. Servant, P. Coulombe, B. Turgeon, and S. Meloche Differential Regulation of P27Kip1 Expression by Mitogenic and Hypertrophic Factors: Involvement of Transcriptional and Posttranscriptional Mechanisms J. Cell Biol., February 7, 2000; 148(3): 543 - 556. [Abstract] [Full Text] [PDF]

				G. GAMBARO and F. J. VAN DER WOUDE Glycosaminoglycans: Use in Treatment of DiabeticNephropathy J. Am. Soc. Nephrol., February 1, 2000; 11(2): 359 - 368. [Full Text] [PDF]

				S. B. Parker, A. D. Dobrian, S. S. Wade, and R. L. Prewitt AT1 receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H613 - H622. [Abstract] [Full Text] [PDF]

				D. M Templeton, Y. Zhao, and M. Y. Fan Heterogeneity in the response of vascular smooth muscle to heparin: altered signaling in heparin-resistant cells Cardiovasc Res, January 14, 2000; 45(2): 503 - 512. [Abstract] [Full Text] [PDF]

				E. Samain, H. Bouillier, S. Miserey, C. Perret, J.-F. Renaud, M. Safar, and G. Dagher Extracellular Signal-Regulated Kinase Pathway Is Involved in Basic Fibroblast Growth Factor Effect on Angiotensin II-Induced Ca2+ Transient in Vascular Smooth Muscle Cell From Wistar-Kyoto and Spontaneously Hypertensive Rats Hypertension, January 1, 2000; 35(1): 61 - 67. [Abstract] [Full Text] [PDF]

				T. Yamakawa, S.-i. Tanaka, K. Numaguchi, Y. Yamakawa, E. D. Motley, S. Ichihara, and T. Inagami Involvement of Rho-Kinase in Angiotensin II-Induced Hypertrophy of Rat Vascular Smooth Muscle Cells Hypertension, January 1, 2000; 35(1): 313 - 318. [Abstract] [Full Text] [PDF]

				B. Andersson, I. Blange, and C. Sylven Angiotensin-II type 1 receptor gene polymorphism and long-term survival in patients with idiopathic congestive heart failure Eur J Heart Fail, December 17, 1999; 1(4): 363 - 369. [Abstract] [Full Text] [PDF]

				T. Hayek, J. Attias, R. Coleman, S. Brodsky, J. Smith, J. L. Breslow, and S. Keidar The angiotensin-converting enzyme inhibitor, fosinopril, and the angiotensin II receptor antagonist, losartan, inhibit LDL oxidation and attenuate atherosclerosis independent of lowering blood pressure in apolipoprotein E deficient mice Cardiovasc Res, December 1, 1999; 44(3): 579 - 587. [Abstract] [Full Text] [PDF]