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      The Effects of Antihypertensive Agents on Atherosclerosis-Related Parameters of Human Aorta Intimal Cells

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          Abstract

          Four antihypertensive agents – amlodipine, verapamil, propranolol and perindoprilat – were studied in human cell cultures. Antiatherogenic activity was investigated using uninvolved human aortic smooth muscle intima cells and atherogenic serum obtained from patients with coronary atherosclerosis. Amlodipine and verapamil significantly inhibited serum-induced increases in cholesterol content, cell-proliferative activity and protein synthesis in the cultured cells. Propranolol increased all three parameters, while perindoprilat had no effects. In addition, amlodipine and verapamil significantly lowered the intracellular cholesterol content of smooth muscle cells derived from atherosclerotic plaque and inhibited cell proliferation and protein synthesis. Propranolol increased all of these parameters, while perindoprilat produced no effects. The antiatherogenic and antiatherosclerotic actions of verapamil and amlodipine were confirmed in an ex vivo model. These studies demonstrated a beneficial antiatherosclerotic effect of amlodipine that was greater than that of verapamil. Perindoprilat had a neutral effect on atherosclerotic parameters, while the action of propranolol appeared to be potentially detrimental.

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          Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial.

          To compare the rate of progression of mean maximum intimal-medial thickness (IMT) in carotid arteries, using quantitative B-mode ultrasound imaging, during antihypertensive therapy with isradipine vs hydrochlorothiazide. Randomized, double-blind, positive-controlled trial. Nine medical center clinics. A total of 883 patients with baseline mean +/- SD systolic and diastolic blood pressure (SBP and DBP, respectively) of 149.7 +/- 16.6 and 96.5 +/- 5.1 mm Hg, age of 58.5 +/- 8.5 years, and maximum IMT of 1.17 +/- 0.20 mm. Twice daily doses of isradipine (2.5-5.0 mg) or hydrochlorothiazide (12.5-25 mg). MAIN OUTCOME MEASURE (PRIMARY END POINT): Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years. There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years (P=.68). There was a higher incidence of major vascular events (eg, myocardial infarction, stroke, congestive heart failure, angina, and sudden death) in isradipine (n=25; 5.65%) vs hydrochlorothiazide (n=14; 3.17%) (P=.07), and a significant increase in nonmajor vascular events and procedures (eg, transient ischemic attack, dysrhythmia, aortic valve replacement, and femoral popliteal bypass graft) in isradipine (n=40; 9.05%) vs hydrochlorothiazide (n=23; 5.22%) (P=.02). At 6 months, mean DBP decreased by 13.0 mm Hg in both groups, and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine (P=.002); the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine. The rate of progression of mean maximum IMT in carotid arteries, the surrogate end point in this study, did not differ between the 2 treatment groups. The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further.
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            Retardation of angiographic progression of coronary artery disease by nifedipine

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              Stellate cells of aortic intima: II. Arborization of intimal cells in culture

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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                1998
                January 1998
                13 February 1998
                : 89
                : 2
                : 111-118
                Affiliations
                Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia
                Article
                6765 Cardiology 1998;89:111–118
                10.1159/000006765
                9524011
                cd726f65-2242-4726-a216-9efaf789d240
                © 1998 S. Karger AG, Basel

                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
                Page count
                Figures: 8, References: 25, Pages: 8
                Categories
                General Cardiology, Basic Science

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Amlodipine,Verapamil,Propranolol,Perindoprilat,Antiatherogenic effect,Antiatherosclerotic effect

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