This Article 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 Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Janiak, P. Articles by Vilaine, J. P. Search for Related Content PubMed PubMed Citation Articles by Janiak, P. Articles by Vilaine, J. P.

Hypertension, Vol 24, 671-678, Copyright © 1994 by American Heart Association

ARTICLES

Role of the renin-angiotensin system in neointima formation after injury in rabbits

P Janiak, O Libert and JP Vilaine
Institut de Recherches Servier, Suresnes, France.

We investigated the role of the renin-angiotensin system in neointima formation in a species in which converting enzyme inhibitors have been so far ineffective in suppressing abnormal vascular repair. The effects of converting enzyme inhibition by perindopril and selective blockade of angiotensin subtype 1 receptor by DuP 753 were assessed on neointima formation after balloon injury of rabbit carotid artery. Myointimal growth was measured by histomorphometric analysis. In rabbits treated 6 days before and for 14 days after injury, perindopril (2 mg/kg per day PO, n = 7) significantly reduced neointima formation (-51%, P < .01). DuP 753 (1 mg/d, n = 8) infused perivascularly for 14 days in the vicinity of injured carotid artery also markedly suppressed myointimal thickening (-60%, P < .01). To determine whether angiotensin subtype 2 receptor was implicated in this vascular response, we infused CGP 42112A, a specific subtype 2 receptor ligand, continuously for 14 days according to the same protocol of DuP 753 administration. CGP 42112A (1 mg/d) did not change the neointima-media ratio, indicating that angiotensin subtype 2 receptors were not involved in myointimal hyperplasia in rabbits. Thus in rabbits, the renin-angiotensin system plays a major role in neointima formation, and the protective effect of perindopril appears to be mediated mainly by inhibition of angiotensin II production, because blockade of the subtype 1 receptor reduced myointimal growth in a manner similar to that of converting enzyme inhibition and because intracarotid infusion of angiotensin II (500 ng/min) at the site of injury enhanced the vascular response (+39%, P < .05). Bradykinin (500 ng/min) administered in the same conditions as angiotensin II did not modify neointima formation.

This article has been cited by other articles:

				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]

				H. Eto, S. Biro, M. Miyata, H. Kaieda, H. Obata, T. Kihara, K. Orihara, and C. Tei Angiotensin II type 1 receptor participates in extracellular matrix production in the late stage of remodeling after vascular injury Cardiovasc Res, July 1, 2003; 59(1): 200 - 211. [Abstract] [Full Text] [PDF]

				N. Hosomi, K. Mizushige, H. Ohyama, T. Takahashi, M. Kitadai, Y. Hatanaka, H. Matsuo, M. Kohno, and J. A. Koziol Angiotensin-Converting Enzyme Inhibition With Enalapril Slows Progressive Intima-Media Thickening of the Common Carotid Artery in Patients With Non-Insulin-Dependent Diabetes Mellitus Stroke, July 1, 2001; 32(7): 1539 - 1545. [Abstract] [Full Text] [PDF]

				Tong Chuang Feng, Wang Yui Ying, Ren Jang Hua, Y. Y Ji, and M. de Gasparo Effect of valsartan and captopril in rabbit carotid injury. Possible involvement of bradykinin in the antiproliferative action of the renin-angiotensin blockade Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1): 19 - 24. [Abstract] [PDF]

				T. J. Anderson, E. Elstein, H. Haber, and F. Charbonneau Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study) J. Am. Coll. Cardiol., January 1, 2000; 35(1): 60 - 66. [Abstract] [Full Text] [PDF]

				B. Yang, D. Li, M I. Phillips, P. Mehta, and J. L Mehta Myocardial angiotensin II receptor expression and ischemia-reperfusion injury Vascular Medicine, May 1, 1998; 3(2): 121 - 130. [Abstract] [PDF]

				F. Elijovich, H.-W. Zhao, C. L. Laffer, Y. Du, D. J. DiPette, T. Inagami, and D. H. Wang Regulation of Growth of the Adrenal Gland in DOC-Salt Hypertension: Role of Angiotensin II Receptor Subtypes Hypertension, January 1, 1997; 29(1): 408 - 413. [Abstract] [Full Text] [PDF]

				E. M. van Kleef, J. Fingerle, and M. J.A.P. Daemen Angiotensin II-Induced Progression of Neointimal Thickening in the Balloon-Injured Rat Carotid Artery Is AT1 Receptor Mediated Arterioscler Thromb Vasc Biol, July 1, 1996; 16(7): 857 - 863. [Abstract] [Full Text]

				N. Bardy, R. Merval, J. Benessiano, J.-L. Samuel, and A. Tedgui Pressure and Angiotensin II Synergistically Induce Aortic Fibronectin Expression in Organ Culture Model of Rabbit Aorta: Evidence for a Pressure-Induced Tissue Renin-Angiotensin System Circ. Res., July 1, 1996; 79(1): 70 - 78. [Abstract] [Full Text]

				Y.-Q. Chen, D. M. Gilliam, B. Rydzewski, and A. J. Naftilan Multiple Enhancer Elements Mediate Induction of c-fos in Vascular Smooth Muscle Cells Hypertension, June 1, 1996; 27(6): 1224 - 1233. [Abstract] [Full Text]

				A. D. Hamdan, W. C. Quist, J. B. Gagne, and E. P. Feener Angiotensin-Converting Enzyme Inhibition Suppresses Plasminogen Activator Inhibitor-1 Expression in the Neointima of Balloon-Injured Rat Aorta Circulation, March 15, 1996; 93(6): 1073 - 1078. [Abstract] [Full Text]