This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 deBlois, D. Articles by Schwartz, S.M. Search for Related Content PubMed PubMed Citation Articles by deBlois, D. Articles by Schwartz, S.M.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:1130-1137.)
© 1996 American Heart Association, Inc.

Articles

Smooth Muscle DNA Replication in Response to Angiotensin II Is Regulated Differently in the Neointima and Media at Different Times After Balloon Injury in the Rat Carotid Artery

Role of AT₁ Receptor Expression

D. deBlois; M. Viswanathan; J.E. Su; A.W. Clowes; J.M. Saavedra; S.M. Schwartz

the Department of Pathology (D. deB., J.E.S., S.M.S.) and Surgery (A.W.C.), University of Washington, Seattle, and the Section on Pharmacology (M.V., J.M.S.), Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Md.

Correspondence to Dr D. deBlois, Centre de Recherche Hotel-Dieu de Montreal, 3840 St Urbain St, Montreal, Quebec H2W 1T8, Canada. E-mail debloisd@ere.umontreal.ca.

We have reported that angiotensin II (Ang II) infusion to rats during the third and fourth weeks after vascular injury stimulates DNA replication in a larger proportion of smooth muscle cells (SMCs) in the arterial neointima than in the underlying media or the normal arterial media. Whether this increased responsiveness to Ang II is a transient or stable property of neointimal cells after vascular injury remained unclear. The present study examined smooth muscle DNA replication in response to Ang II infusion (250 ng·kg^-1·min^-1 for 2 weeks) at 3 to 4, 9 to 10, or 27 to 28 weeks after balloon injury to the rat carotid artery. Control rats received Ringer's lactate. BrdU (0.8 mg·kg^-1·d^-1) was coinfused to label replicating DNA. The increased replicative response to Ang II in the neointima versus the normal arterial media did not persist beyond the period of rapid lesion growth shortly after injury, even in neointimal areas without endothelial regeneration. By 9 to 10 weeks after injury, replication frequencies were comparable in the neointima and the normal arterial wall. In the presence of a regenerated endothelium, neointimal DNA replication was lowered but not abolished. After the early period, however, the most marked difference may be the loss of ability of medial SMCs to respond mitogenically to systemic Ang II. As a consequence, Ang II–induced DNA replication in injured arteries was greater in the neointima than in the underlying media at all times studied after injury. DNA replication levels correlated with AT₁ receptor levels in the injured artery neointima but not media, as shown by receptor binding in vascular sections at 3 and 10 weeks after injury. The growth response to systemic Ang II is differentially regulated in adjacent smooth muscle layers in the injured arterial wall in vivo via mechanisms that include, but are not restricted to, the regulation of AT₁ receptor expression in SMCs.

Key Words: vascular smooth muscle • DNA replication • angiotensin II receptors • neointima

This article has been cited by other articles:

				J.-H. Parmentier, C. Zhang, A. Estes, S. Schaefer, and K. U. Malik Essential role of PKC-{zeta} in normal and angiotensin II-accelerated neointimal growth after vascular injury Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1602 - H1613. [Abstract] [Full Text] [PDF]

				J.-L. Bascands, J.-P. Girolami, M. Troly, I. Escargueil-Blanc, D. Nazzal, R. Salvayre, and N. Blaes Angiotensin II Induces Phenotype-Dependent Apoptosis in Vascular Smooth Muscle Cells Hypertension, December 1, 2001; 38(6): 1294 - 1299. [Abstract] [Full Text] [PDF]

				J. Ibrahim, A. D. Hughes, and P. S. Sever Action of Angiotensin II on DNA Synthesis by Human Saphenous Vein in Organ Culture Hypertension, November 1, 2000; 36(5): 917 - 921. [Abstract] [Full Text] [PDF]

				B.-S. Tea, S. Der Sarkissian, R. M. Touyz, P. Hamet, and D. deBlois Proapoptotic and Growth-Inhibitory Role of Angiotensin II Type 2 Receptor in Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats In Vivo Hypertension, May 1, 2000; 35(5): 1069 - 1073. [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]

				M. Roque, J. T. Fallon, J. J. Badimon, W. X. Zhang, M. B. Taubman, and E. D. Reis Mouse Model of Femoral Artery Denudation Injury Associated With the Rapid Accumulation of Adhesion Molecules on the Luminal Surface and Recruitment of Neutrophils Arterioscler Thromb Vasc Biol, February 1, 2000; 20(2): 335 - 342. [Abstract] [Full Text] [PDF]

				Y. Funakoshi, T. Ichiki, K. Ito, and A. Takeshita Induction of Interleukin-6 Expression by Angiotensin II in Rat Vascular Smooth Muscle Cells Hypertension, July 1, 1999; 34(1): 118 - 125. [Abstract] [Full Text] [PDF]

				S. Tazawa, T. Nakane, and S. Chiba Angiotensin II Type 1 Receptor Blockade Prevents Up-Regulation of Angiotensin II Type 1A Receptors in Rat Injured Artery J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 898 - 904. [Abstract] [Full Text]

				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]

				M. G. Melaragno, D. A. Wuthrich, V. Poppa, D. Gill, V. Lindner, B. C. Berk, and M. A. Corson Increased Expression of Axl Tyrosine Kinase After Vascular Injury and Regulation by G Protein–Coupled Receptor Agonists in Rats Circ. Res., October 5, 1998; 83(7): 697 - 704. [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]

				D. deBlois, D. M. Lombardi, E. J. Su, A. W. Clowes, S. M. Schwartz, and C. M. Giachelli Angiotensin II Induction of Osteopontin Expression and DNA Replication in Rat Arteries Hypertension, December 1, 1996; 28(6): 1055 - 1063. [Abstract] [Full Text]

				D. deBlois, S.M. Schwartz, E.M. van Kleef, J.E. Su, K.A. Griffin, A.K. Bidani, M.J.A.P. Daemen, and D.M. Lombardi Chronic {alpha}1-Adrenoreceptor Stimulation Increases DNA Synthesis in Rat Arterial Wall: Modulation of Responsiveness After Vascular Injury Arterioscler Thromb Vasc Biol, September 1, 1996; 16(9): 1122 - 1129. [Abstract] [Full Text]