This Article Full Text 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 Fernandez-Alfonso, M. S. Articles by Paul, M. Search for Related Content PubMed PubMed Citation Articles by Fernandez-Alfonso, M. S. Articles by Paul, M.

(Hypertension. 1997;30:272-277.)
© 1997 American Heart Association, Inc.

Articles

Early Induction of Angiotensin I–Converting Enzyme in Rat Carotid Artery After Balloon Injury

Maria S. Fernandez-Alfonso; Piero A. Martorana; Ivo Licka; Paul van Even; Dieter Trobisch; Bernward A. Schölkens; ; Martin Paul

From the Departamento de Farmacologia, Facultad de Farmacia, Universidad Complutense, Madrid, Spain (M.S.F.-A.); Hoechst Marion Roussel, Pharma Forschung HMR TD, Cardiovascular Agents, Frankfurt am Main, Germany (P.A.M., P. van E., D.T., B.A.S.); and the Department of Clinical Pharmacology and Toxicology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany (I.L., M.P.).

Correspondence to Prof Martin Paul, Department of Clinical Pharmacology and Toxicology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail paul{at}ukbf.fu-berlin.de

Abstract Several studies have demonstrated the effectiveness of angiotensin I–converting enzyme (ACE) inhibitors in preventing the neointima formation found after denudation of the rat carotid artery by balloon injury. The aim of the present study was to determine the role of ACE in this model and to compare the treatment with the ACE inhibitor ramiprilat with that with the angiotensin II antagonist HR 720. The endothelial layer of the left carotid artery was removed using an inflated balloon catheter. Injured and control vessels were both submitted to histomorphological analysis and DNA content quantification at 2, 4, 6, 8, 12, and 14 days after injury. Evaluation of neointima thickening demonstrated a slow but steady increase of neointima that was significant after day 6 and reached 30% of the lumen in 2 weeks. This was paralleled by an increase in DNA content, which was significant 4 days after injury. ACE mRNA levels were quantified by polymerase chain reaction after reverse transcription. Measurement of ACE mRNA levels revealed a significant upregulation 2 and 8 days after injury, with no significant difference when compared with control tissue at later time points. ACE activity was also significantly enhanced at 2 and 8 days after injury, with no significant difference when compared with control tissue at later time points. In addition, the treatment with ramiprilat was more efficient in reducing neointima formation than that with HR 720. These data underlie the role of ACE in this model of restenosis. The early induction of ACE expression after endothelial injury but before significant changes in the vessel structure suggests that ACE activity might be one of the mechanisms that trigger neointima formation in the rat.

Key Words: angiotensin-converting enzyme inhibitors • angiotensin-converting enzyme • balloon injury • polymerase chain reaction

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]

				R. K. Dubey and E. K. Jackson Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms Am J Physiol Renal Physiol, March 1, 2001; 280(3): F365 - F388. [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]