This Article Full Text 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 Zhuo, J. L. Articles by Ohishi, M. Search for Related Content PubMed PubMed Citation Articles by Zhuo, J. L. Articles by Ohishi, M. Related Collections Cardio-renal physiology/pathophysiology Cardiovascular Pharmacology ACE/Angiotension receptors Peripheral vascular disease Chronic ischemic heart disease Endothelium/vascular type/nitric oxide Mechanism of atherosclerosis/growth factors

(Hypertension. 2002;39:634.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

Jia Long Zhuo; Frederick A.O. Mendelsohn; Mitsuru Ohishi

From the Howard Florey Institute, University of Melbourne (J.L.Z., F.A.O.M.), Victoria, Australia; Department of Geriatric Medicine, Osaka University Medical School (M.O.), Osaka, Japan; and Division of Hypertension and Vascular Research, Henry Ford Hospital (J.L.Z.), Detroit, Mich.

Correspondence to Jia L. Zhuo, MD, PhD, Division of Hypertension and Vascular Research, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202-2689. E-mail jzhuo1{at}hfhs.org

Angiotensin-converting enzyme inhibitors (ACEi) reduce cardiovascular morbidity and mortality by improving coronary perfusion, reducing ventricular hypertrophy and remodeling, and preventing progression of coronary atherosclerosis. However, the cellular mechanisms underlying the beneficial effects of ACEi are not fully understood. We studied the in vivo effects of ACE inhibition with perindopril on cellular expression of ACE, AT₁ receptors and 2 nitric oxide synthase (NOS) isoforms, endothelial (eNOS) and inducible NOS (iNOS), in human blood vessels using quantitative in vitro autoradiography and immunocytochemistry. Seven patients with ischemic heart disease were treated with perindopril (4 mg/d) for up to 5 weeks before elective coronary bypass surgery, whereas controls did not receive the ACEi (n=7). Perindopril decreased plasma ACE by 70% and the plasma angiotensin II to angiotensin I ratio by 57% and reduced vascular ACE to approximately 65% of control levels in both endothelium and adventitia. By contrast, AT₁ receptor binding in vascular smooth muscle cells was increased by 80% in patients treated with perindopril as confirmed by immunocytochemistry. eNOS was expressed primarily in endothelial cells, whereas little iNOS expression occurred in vascular smooth muscle cells of untreated patients. Both eNOS and iNOS expression seemed to increase during perindopril treatment. These results suggest that suppression of angiotensin II formation in the vascular wall and increased expression of eNOS and iNOS during ACE inhibition may be beneficial in reversing endothelial dysfunction in patients with cardiovascular disease. Because vascular AT₁ receptor expression is increased during chronic ACE inhibition, more clinical studies are required to determine whether it is necessary to combine ACE inhibitors and AT₁ receptor antagonists in clinical management of heart failure, coronary heart disease, and hypertension

Key Words: angiotensin-converting enzyme • angiotensin II • atherosclerosis • coronary artery disease • ACE inhibitor • nitric oxide synthase

This article has been cited by other articles:

				R. Donnelly and G. Manning Review: Angiotensin-converting enzyme inhibitors and coronary heart disease prevention Journal of Renin-Angiotensin-Aldosterone System, March 1, 2007; 8(1): 13 - 22. [Abstract] [PDF]

				C. Ceconi, K. M. Fox, W. J. Remme, M. L. Simoons, M. Bertrand, G. Parrinello, C. Kluft, A. Blann, D. Cokkinos, and R. Ferrari ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT Cardiovasc Res, January 1, 2007; 73(1): 237 - 246. [Abstract] [Full Text] [PDF]

				H. Morawietz, S. Erbs, J. Holtz, A. Schubert, M. Krekler, W. Goettsch, O. Kuss, V. Adams, K. Lenk, F. W. Mohr, et al. Endothelial Protection, AT1 Blockade and Cholesterol-Dependent Oxidative Stress: The EPAS Trial Circulation, July 4, 2006; 114(1_suppl): I-296 - I-301. [Abstract] [Full Text] [PDF]

				F. Ribichini, F. Pugno, V. Ferrero, G. Bussolati, M. Feola, P. Russo, C. Di Mario, A. Colombo, and C. Vassanelli Cellular Immunostaining of Angiotensin-Converting Enzyme in Human Coronary Atherosclerotic Plaques J. Am. Coll. Cardiol., March 21, 2006; 47(6): 1143 - 1149. [Abstract] [Full Text] [PDF]

				T. S. Hermann, W. Li, H. Dominguez, N. Ihlemann, C. Rask-Madsen, A. Major-Pedersen, D. B. Nielsen, K. W. Hansen, M. Hawkins, L. Kober, et al. Quinapril Treatment Increases Insulin-Stimulated Endothelial Function and Adiponectin Gene Expression in Patients with Type 2 Diabetes J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1001 - 1008. [Abstract] [Full Text] [PDF]

				G. Heinze, C. Mitterbauer, H. Regele, R. Kramar, W. C. Winkelmayer, G. C. Curhan, and R. Oberbauer Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Type 1 Receptor Antagonist Therapy Is Associated with Prolonged Patient and Graft Survival after Renal Transplantation J. Am. Soc. Nephrol., March 1, 2006; 17(3): 889 - 899. [Abstract] [Full Text] [PDF]

				V. L. Sales, G. K. Sukhova, M. A. Lopez-Ilasaca, P. Libby, V. J. Dzau, and R. E. Pratt Angiotensin Type 2 Receptor Is Expressed in Murine Atherosclerotic Lesions and Modulates Lesion Evolution Circulation, November 22, 2005; 112(21): 3328 - 3336. [Abstract] [Full Text] [PDF]

				B. Jiang, S. Xu, X. Hou, D. R. Pimentel, and R. A. Cohen Angiotensin II Differentially Regulates Interleukin-1-{beta}-inducible NO Synthase (iNOS) and Vascular Cell Adhesion Molecule-1 (VCAM-1) Expression: ROLE OF p38 MAPK J. Biol. Chem., May 7, 2004; 279(19): 20363 - 20368. [Abstract] [Full Text] [PDF]

				A. Schafer, D. Fraccarollo, P. Tas, I. Schmidt, G. Ertl, and J. Bauersachs Endothelial dysfunction in congestive heart failure: ACE inhibition vs. angiotensin II antagonism Eur J Heart Fail, March 1, 2004; 6(2): 151 - 159. [Abstract] [Full Text] [PDF]

				K. Fox Poststroke patients: implications for the cardiologist Eur. Heart J. Suppl., July 1, 2003; 5(suppl_E): E4 - E10. [Abstract] [PDF]

				A. Schafer, D. Fraccarollo, S. K Hildemann, P. Tas, G. Ertl, and J. Bauersachs Addition of the selective aldosterone receptor antagonist eplerenone to ACE inhibition in heart failure: effect on endothelial dysfunction Cardiovasc Res, June 1, 2003; 58(3): 655 - 662. [Abstract] [Full Text] [PDF]

				F. Ribichini, V. Ferrero, W. Wijns, G. Matullo, A. Piazza, E. Uslenghi, J. L. Zhuo, F. A.O. Mendelsohn, and M. Ohishi Can ACE Inhibitors Promote Detrimental Vascular Effects After Percutaneous Injury? * Response Hypertension, October 1, 2002; e6(4): . [Full Text] [PDF]