Circulation Research, Vol 68, 450-456, Copyright © 1991 by American Heart Association

ARTICLES

Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall

MJ Daemen, DM Lombardi, FT Bosman and SM Schwartz
Department of Pathology, University of Limburg, Maastricht, The Netherlands.

The present study was undertaken to explore the possibility that neointimal smooth muscle cells, the characteristic cells of restenosis and atherosclerosis, are selectively stimulated to replicate by a hypertensive stimulus. Angiotensin II (AII) was infused by osmotic minipumps for 2 weeks in 4.5-month-old rats. Group A received AII (200 ng/min) 2 weeks after a balloon catheter-induced injury of the thoracic aorta and left common carotid artery. Group B received only AII, group C only balloon denudation, and group D neither balloon injury nor AII. During the AII or Ringer's solution infusion, all animals received [3H]thymidine via a second minipump to measure DNA synthesis. AII increased the systolic pressure by more than 40 mm Hg. AII significantly increased DNA synthesis in the media of the carotid artery from 0.2 +/- 0.2% in group C to 2.5 +/- 1.5% in group A (mean +/- SD, n = 5 or 6). DNA synthesis in the neointima of the carotid artery significantly increased with AII from 4.8 +/- 4.2% in group C to 19.8 +/- 13.9% in group A. Cross-sectional area of the neointima almost doubled during AII infusion, and it increased approximately 25% in the media. Comparable results were obtained in the aorta. In a second experiment, AII was infused (125 ng/min) for 2 weeks in 11-week-old rats. Concomitantly, [3H]thymidine was given. Control rats received Ringer's solution and [3H]thymidine in their pumps. Blood pressures were elevated to the same extent as in the older animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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				K. Fujii, S. Umemoto, A. Fujii, T. Yonezawa, T. Sakumura, and M. Matsuzaki Angiotensin II Type 1 Receptor Antagonist Downregulates Nonmuscle Myosin Heavy Chains in Spontaneously Hypertensive Rat Aorta Hypertension, April 1, 1999; 33(4): 975 - 980. [Abstract] [Full Text] [PDF]

				H. G Hutchinson, L. Hein, M. Fujinaga, and R. E Pratt Modulation of vascular development and injury by angiotensin II Cardiovasc Res, March 1, 1999; 41(3): 689 - 700. [Abstract] [Full Text] [PDF]

				Y. Furukawa, A. Matsumori, N. Ohashi, T. Shioi, K. Ono, A. Harada, K. Matsushima, and S. Sasayama Anti–Monocyte Chemoattractant Protein-1/Monocyte Chemotactic and Activating Factor Antibody Inhibits Neointimal Hyperplasia in Injured Rat Carotid Arteries Circ. Res., February 19, 1999; 84(3): 306 - 314. [Abstract] [Full Text] [PDF]

				K. Harada, I. Komuro, T. Sugaya, K. Murakami, and Y. Yazaki Vascular Injury Causes Neointimal Formation in Angiotensin II Type 1a Receptor Knockout Mice Circ. Res., February 5, 1999; 84(2): 179 - 185. [Abstract] [Full Text] [PDF]

				P. E. McEwan, G. P. Vinson, and C. J. Kenyon Control of adrenal cell proliferation by AT1 receptors in response to angiotensin II and low-sodium diet Am J Physiol Endocrinol Metab, February 1, 1999; 276(2): E303 - E309. [Abstract] [Full Text] [PDF]

				S. K. Sharma, D. Chapman, R. Temsah, T. Netticadan, D. P. Brasil, and N. S. Dhalla Prevention of Vascular Apoptosis in Myocardial Infarction by Losartan Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(2): 77 - 84. [Abstract] [PDF]

				X.-P. Xi, K. Graf, S. Goetze, E. Fleck, W. A. Hsueh, and R. E. Law Central Role of the MAPK Pathway in Ang II–Mediated DNA Synthesis and Migration in Rat Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, January 1, 1999; 19(1): 73 - 82. [Abstract] [Full Text] [PDF]

				W. B. Strawn, C. M. Ferrario, and E. A. Tallant Angiotensin-(1–7) Reduces Smooth Muscle Growth After Vascular Injury Hypertension, January 1, 1999; 33(1): 207 - 211. [Abstract] [Full Text] [PDF]

				P. E. McEwan, G. A. Gray, L. Sherry, D. J. Webb, and C. J. Kenyon Differential Effects of Angiotensin II on Cardiac Cell Proliferation and Intramyocardial Perivascular Fibrosis In Vivo Circulation, December 15, 1998; 98(24): 2765 - 2773. [Abstract] [Full Text] [PDF]

				M. K. Magnusson and D. F. Mosher Fibronectin : Structure, Assembly, and Cardiovascular Implications Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1363 - 1370. [Full Text] [PDF]

				B. C. Yang, M. I. Phillips, D. Mohuczy, H. Meng, L. Shen, P. Mehta, and J. L. Mehta Increased Angiotensin II Type 1 Receptor Expression in Hypercholesterolemic Atherosclerosis in Rabbits Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1433 - 1439. [Abstract] [Full Text] [PDF]

				Y. Higashi, T. Oshima, S. Sasaki, Y. Nakano, M. Kambe, H. Matsuura, and G. Kajiyama Angiotensin-Converting Enzyme Inhibition, But Not Calcium Antagonism, Improves a Response of the Renal Vasculature to L-Arginine in Patients With Essential Hypertension Hypertension, July 1, 1998; 32(1): 16 - 24. [Abstract] [Full Text] [PDF]

				E. J. Su, D. M. Lombardi, J. Siegal, and S. M. Schwartz Angiotensin II Induces Vascular Smooth Muscle Cell Replication Independent of Blood Pressure Hypertension, June 1, 1998; 31(6): 1331 - 1337. [Abstract] [Full Text] [PDF]

				J. P. O'Malley, J. P. BS, C. L. Maslen, and D. R. Illingworth Angiotensin-Converting Enzyme DD Genotype and Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia Circulation, May 19, 1998; 97(18): 1780 - 1783. [Abstract] [Full Text] [PDF]

				W. Huang, F. A. Gelas, and M. J. Osborne-Pellegrin Protection of the Arterial Internal Elastic Lamina by Inhibition of the Renin-Angiotensin System in the Rat Circ. Res., May 4, 1998; 82(8): 879 - 890. [Abstract] [Full Text] [PDF]

				S. Seewald, C. Seul, R. Kettenhofen, D. Bokemeyer, Y. Ko, H. Vetter, and A. Sachinidis Role of Mitogen-Activated Protein Kinase in the Angiotensin II–Induced DNA Synthesis in Vascular Smooth Muscle Cells Hypertension, May 1, 1998; 31(5): 1151 - 1156. [Abstract] [Full Text] [PDF]

				N. J. Brown and D. E. Vaughan Angiotensin-Converting Enzyme Inhibitors Circulation, April 14, 1998; 97(14): 1411 - 1420. [Abstract] [Full Text] [PDF]

				H. Koyama, N. E. Olson, F. F. Dastvan, and M. A. Reidy Cell Replication in the Arterial Wall : Activation of Signaling Pathway Following In Vivo Injury Circ. Res., April 6, 1998; 82(6): 713 - 721. [Abstract] [Full Text] [PDF]

				E. Van Belle, C. Bauters, T. Asahara, and J. M. Isner Endothelial regrowth after arterial injury: from vascular repair to therapeutics Cardiovasc Res, April 1, 1998; 38(1): 54 - 68. [Full Text] [PDF]

				R. J. Dilley and M. I. Nataatmadja Heparin inhibits mesenteric vascular hypertrophy in angiotensin II-infusion hypertension in rats Cardiovasc Res, April 1, 1998; 38(1): 247 - 255. [Abstract] [Full Text] [PDF]

				B. Fisslthaler, V. B Schini-Kerth, I. Fleming, and R. Busse Thrombin receptor expression is increased by angiotensin II in cultured and native vascular smooth muscle cells Cardiovasc Res, April 1, 1998; 38(1): 263 - 271. [Abstract] [Full Text] [PDF]

				A. Otani, H. Takagi, K. Suzuma, and Y. Honda Angiotensin II Potentiates Vascular Endothelial Growth Factor–Induced Angiogenic Activity in Retinal Microcapillary Endothelial Cells Circ. Res., March 23, 1998; 82(5): 619 - 628. [Abstract] [Full Text] [PDF]

				E. J. Su, D. M. Lombardi, J. Wiener, M. J. A. P. Daemen, M. A. Reidy, and S. M. Schwartz Mitogenic Effect of Angiotensin II on Rat Carotid Arteries and Type II or III Mesenteric Microvessels but Not Type I Mesenteric Microvessels Is Mediated by Endogenous Basic Fibroblast Growth Factor Circ. Res., February 23, 1998; 82(3): 321 - 327. [Abstract] [Full Text] [PDF]