This Article Full Text Full Text (PDF) All Versions of this Article: 45/6/1194    most recent 01.HYP.0000168945.44069.aav1 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 Ahimastos, A. A. Articles by Kingwell, B. A. Search for Related Content PubMed PubMed Citation Articles by Ahimastos, A. A. Articles by Kingwell, B. A. Related Collections ACE/Angiotension receptors Peripheral vascular disease Clinical Studies

(Hypertension. 2005;45:1194.)
© 2005 American Heart Association, Inc.

Original Articles

Ramipril Reduces Large-Artery Stiffness in Peripheral Arterial Disease and Promotes Elastogenic Remodeling in Cell Culture

Anna A. Ahimastos; Alaina K. Natoli; Adam Lawler; Peter A. Blombery; Bronwyn A. Kingwell

From the Alfred and Baker Medical Unit, Baker Heart Research Institute, Melbourne, Victoria, Australia.

Correspondence to Bronwyn Kingwell, Alfred and Baker Medical Unit, Baker Medical Research Institute, P.O. Box 6492, St Kilda Road Central, Melbourne, Victoria, 8008, Australia. E-mail b.kingwell{at}alfred.org.au

Ramipril improves cardiovascular outcome in patients with peripheral arterial disease; however, the precise mechanisms of benefit remain to be elucidated. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined. In addition, we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture. Forty patients with peripheral arterial disease were randomized to receive ramipril, 10 mg once daily or placebo for 24 weeks. Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index (carotid tonometry and Doppler velocimetry), and regionally via carotid–femoral pulse wave velocity. Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10±0.02 mL/mm Hg, (P<0.001, all probability values relative to placebo) and reduced pulse wave velocity by 1.7±0.2 m/s (P<0.001), augmentation index by 4.1±0.3% (P<0.001), and systolic blood pressure by 5±1 mm Hg (P<0.001). Ramipril did not reduce mean arterial pressure significantly compared with placebo (P=0.59). In cell culture, ramiprilat decreased collagen deposition by >50% and increased elastin and fibrillin-1 deposition by >3- and 4-fold respectively (histochemistry and immunohistochemistry). Fibrillin-1 gene expression was increased 5-fold (real-time reverse-transcriptase polymerase chain reaction). Ramiprilat also reduced gene and protein (Western) expression of both matrix metalloproteinase (MMP)-2 and MMP-3. In conclusion, ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation, which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease.

Key Words: angiotensin-converting enzyme • arteries • extracellular matrix

This article has been cited by other articles:

				J. E. Wagenseil and R. P. Mecham Vascular Extracellular Matrix and Arterial Mechanics Physiol Rev, July 1, 2009; 89(3): 957 - 989. [Abstract] [Full Text] [PDF]

				J. C. Kaski and G. W. Cockerill STARR (STudy of Atherosclerosis with Ramipril and Rosiglitazone) Is the Biggest Big Enough? J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2036 - 2038. [Full Text] [PDF]

				J. L. Serra and M. Bendersky Review: Atrial fibrillation and renin-angiotensin system Therapeutic Advances in Cardiovascular Disease, June 1, 2008; 2(3): 215 - 223. [Abstract] [PDF]

				A. A. Ahimastos, A. Aggarwal, K. M. D'Orsa, M. F. Formosa, A. J. White, R. Savarirayan, A. M. Dart, and B. A. Kingwell Effect of Perindopril on Large Artery Stiffness and Aortic Root Diameter in Patients With Marfan Syndrome: A Randomized Controlled Trial JAMA, October 3, 2007; 298(13): 1539 - 1547. [Abstract] [Full Text] [PDF]

				S. Heeneman, J. C. Sluimer, and M. J.A.P. Daemen Angiotensin-Converting Enzyme and Vascular Remodeling Circ. Res., August 31, 2007; 101(5): 441 - 454. [Abstract] [Full Text] [PDF]

				G. F. Mitchell, M. E. Dunlap, W. Warnica, A. Ducharme, J. M. O. Arnold, J.-C. Tardif, S. D. Solomon, M. J. Domanski, K. A. Jablonski, M. M. Rice, et al. Long-Term Trandolapril Treatment Is Associated With Reduced Aortic Stiffness: The Prevention of Events With Angiotensin-Converting Enzyme Inhibition Hemodynamic Substudy Hypertension, June 1, 2007; 49(6): 1271 - 1277. [Abstract] [Full Text] [PDF]

				N. Iwai, K. Kajimoto, Y. Kokubo, and H. Tomoike Extensive Genetic Analysis of 10 Candidate Genes for Hypertension in Japanese Hypertension, November 1, 2006; 48(5): 901 - 907. [Abstract] [Full Text] [PDF]

				M. F. O'Rourke and J. B. Seward Central Arterial Pressure and Arterial Pressure Pulse: New Views Entering the Second Century After Korotkov Mayo Clin. Proc., August 1, 2006; 81(8): 1057 - 1068. [Abstract] [Full Text] [PDF]

				R. L. Armentano, J. G. Barra, D. B. Santana, F. M. Pessana, S. Graf, D. Craiem, L. M. Brandani, H. P. Baglivo, and R. A. Sanchez Smart Damping Modulation of Carotid Wall Energetics in Human Hypertension: Effects of Angiotensin-Converting Enzyme Inhibition Hypertension, March 1, 2006; 47(3): 384 - 390. [Abstract] [Full Text] [PDF]

				M. F. O'Rourke, W. W. Nichols, E. O'Brien, B. A. Kingwell, and P. A. Blombery Effects of Ramipril on Arterial Stiffness Hypertension, October 1, 2005; 46(4): e14 - e15. [Full Text] [PDF]