Temocapril, an Angiotensin Converting Enzyme Inhibitor, Ameliorates Age-Related Increase in Carotid Arterial Stiffness in Normotensive Subjects

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Abstract

Background/Aims: Oxidative stress plays an important role in vascular ageing. The close relationship of the renin-angiotensin system with mechanisms of oxidative stress suggests its possible involvement in the deleterious effects of ageing. The present study was designed to investigate whether inhibition of the renin-angiotensin system improves the age-related increase in arterial stiffness. Methods: Normotensive elderly subjects in a geriatric nursing home (n = 24; male/female = 7/17; 86 ± 9 years, mean ± SD) were randomly assigned to receive either an angiotensin converting enzyme inhibitor, temocapril (n = 12, 1 mg daily) or nothing (n = 12). Carot id arterial stiffness parameter β and circulating levels of malondialdehyde-modified low-density lipoprotein were measured before and 6 months after randomization. Results: Temocapril decreased β (from 7.0 ± 1.0 to 4.9 ± 0.9, p < 0.05) and malondialdehyde-modified low-density lipoprotein levels (from 73.2 ± 19.9 to 61.3 ± 18.4 U/l, p < 0.05) without changing the blood pressure. The changes in β and malondialdehyde-modified low-density lipoprotein levels were significantly correlated (ρ = 0.600, p < 0.05). Conclusion: These results suggest that temocapril ameliorates the age-related increase in carotid arterial stiffness in healthy, normotensive elderly subjects.

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Role of oxidative stress in atherosclerosis

David K Harrison, Kathy K. Griendling, Ulf Landmesser … (2003)

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Strategies to reduce oxidative stress in cardiovascular disease.

M Brosnan, Brian W McBride, D. Drummond … (2004)

A multitude of studies in experimental animals, together with clinical data, provide evidence that increased production of ROS (reactive oxygen species) are involved in the development and progression of cardiovascular disease. As ROS appear to have a critical role in atherosclerosis, there has been considerable interest in identifying the enzyme systems involved and in developing strategies to reduce oxidative stress. Prospective clinical trials with vitamins and hormone replacement therapy have not fulfilled earlier promises, although there is still interest in other dietary supplements. Superoxide dismutase mimetics, thiols, xanthine oxidase and NAD(P)H oxidase inhibitors are currently receiving much interest, while animal studies using gene therapy show promise, but are still at an early stage. Of the drugs in common clinical use, there is evidence that ACE (angiotensin-converting enzyme) inhibitors and AT1 (angiotensin II type 1) receptor blockers have beneficial effects on oxidative stress above their antihypertensive properties, whereas statins, in addition to improving lipid profiles, may also lower oxidative stress.

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A new noninvasive measurement system for wave intensity: evaluation of carotid arterial wave intensity and reproducibility.

W A Harada, Takashi Okada, Kiyomi Niki … (2002)

Wave intensity (WI) is a new hemodynamic index that provides information about the dynamic behavior of the heart and the vascular system and their interaction. Carotid arterial wave intensity in normal subjects has two positive peaks. The first peak, W(1), occurs during early systole, the magnitude of which increases with increases in cardiac contractility. The second peak, W(2), which occurs towards the end of ejection, is related to the ability of the left ventricle to actively stop aortic blood flow. Between the two positive peaks, a negative area, NA, is often observed, which signifies reflections from the cerebral circulation. The time interval between the R-wave of ECG and the first peak (R - W(1)) corresponds to the pre-ejection period, and that between the first and second peaks (W(1) - W(2)) corresponds to ejection time. We developed a new ultrasonic on-line system for obtaining WI and arterial stiffness (beta). The purpose of this study was (1) to report normal values of various indices derived from WI and beta measured with this system, and (2) to evaluate the intraobserver and interobserver reproducibility of the measurements. The measurement system is composed of a computer, a WI unit, and an ultrasonic machine. The WI unit gives the instantaneous change in diameter of the artery and the instantaneous mean blood velocity through the sampling gate. Using these parameters and blood pressure measured with a cuff-type manometer, the computer gives WI and beta. We applied this method to the carotid artery in 135 normal subjects. The mean values of W(1), W(2), NA, R - W(1), and W(1) - W(2) were 8 940 +/- 3 790 mmHg m/s(3), 1 840 +/- 880 mmHg m/s(3), 27 +/- 13 mmHg m/s(2), 104 +/- 14 ms, and 270 +/- 19 ms, respectively. These values did not show a significant correlation with age. The mean value of beta was 10.4 +/- 4.8 and the values significantly correlated with age (men: r = 0.66, P < 0.0001; women: r= 0.81, P < 0.0001). The reproducibility was evaluated by intraobserver intrasession (IA), intraobserver intersession (IE), and interobserver intrasession variability (IO). The reproducibility of R - W(1) and W(1) - W(2) was high: the mean coefficient of variation (mCV) of IA was less than 3%; 95% confidence limits from the mean values (CL) were less than 8% for IE and less than 4% for IO. The reproducibility of W(1) and beta was good: mCV for IA was less than 10%; CL for IE and IO were less than 17%. W(2) and NA showed a higher variability than other indices: mCV for IA was less than 13%, and CL for IE and IO were less than 36%. However, two sessions by the same observer and two sessions by different observers were not biased. Wave intensity measurements with this system are clinically acceptable.

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Author and article information

Journal

Journal ID (publisher-id): CRD

Journal ID (nlm-ta): Cardiology

Journal ID (doi): 10.1159/issn.0008-6312

Title: Cardiology

Publisher: S. Karger AG

ISSN (Print): 0008-6312

ISSN (Electronic): 1421-9751

Publication date Subscription-year: 2006

Publication date (Print): September 2006

Publication date (Electronic): 29 September 2006

Volume: 106

Issue: 3

Pages: 190-194

Affiliations

^aDepartment of Internal Medicine, Nagoya Kosein Hospital, and ^bInternal Medicine and Molecular Science, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

Article

Publisher ID: 93024 Other ID: Cardiology 2006;106:190–194

DOI: 10.1159/000093024

PubMed ID: 16675905

SO-VID: 4ce09d14-4b84-4d36-ba30-47d8682add4a

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 23 November 2005

Date accepted : 16 March 2006

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Figures: 3, Tables: 1, References: 28, Pages: 5

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Temocapril, an Angiotensin Converting Enzyme Inhibitor, Ameliorates Age-Related Increase in Carotid Arterial Stiffness in Normotensive Subjects

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Abstract

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Karger: Cardiovascular System

Most cited references 18

Role of oxidative stress in atherosclerosis

Strategies to reduce oxidative stress in cardiovascular disease.

A new noninvasive measurement system for wave intensity: evaluation of carotid arterial wave intensity and reproducibility.

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