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Regression of cardiac hypertrophy in the SHR by combined renin-angiotensin system blockade and dietary sodium restriction

Department of Physiology, University of Melbourne, Parkville, Victoria, 3010, Australia

Cory D Griffiths

Department of Physiology, University of Melbourne, Parkville, Victoria, 3010, Australia

Trefor O Morgan

Department of Physiology, University of Melbourne, Parkville, Victoria, 3010, Australia

Lea MD Delbridge

Department of Physiology, University of Melbourne, Parkville, Victoria, 3010, Australia, l.delbridge{at}physiology.unimelb.edu.au

Altered operation of the renin-angiotensin-aldosterone system (RAAS) and dietary sodium intake have been identified as independent risk factors for cardiac hypertrophy. The way in which sodium intake and the operation of the renin-angiotensin-aldosterone system interact in the pathogenesis of cardiac hypertrophy is poorly understood. The aims of this study were to investigate the cardiac effects of the renin-angiotensin system (RAS) blockade in the spontaneously hypertensive rat (SHR), using co-treatment with an angiotensin II receptor blocker (ARB) and an angiotensin-converting enzyme (ACE) inhibitor with different sodium intakes. Our experiments with SHR show that, at high levels of sodium intake (4.0%), aggressive RAS blockade treatment with candesartan (3 mg/kg) and perindopril (6 mg/kg) does not result in regression of cardiac hypertrophy. In contrast, RAS blockade coupled with reduced sodium diet (0.2%) significantly regresses cardiac hypertrophy, impairs animal growth and is associated with elevated plasma renin and dramatically suppressed plasma angiotensinogen levels. Histological analyses indicate that the differential effect of reduced sodium on heart growth during RAS blockade is not associated with any change in myocardial interstitial collagen, but reflects modification of cellular geometry. Dimensional measurements of enzymatically-isolated ventricular myocytes show that, in the RAS blocked, reduced sodium group, myocyte length and width were decreased by about 16—19% compared with myocytes from the high sodium treatment group. Our findings highlight the importance of `titrating' sodium intake with combined RAS blockade in the clinical setting to optimise therapeutic benefit.

Key Words: angiotensin receptor blocker • angiotensin-converting enzyme inhibitor • cardiac hypertrophy • myocardial fibrosis • cardiomyocyte

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S148-S153 (2001)
DOI: 10.1177/14703203010020012601


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This Article Abstract Free Full Text (Free PDF) Free 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 Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Abro, E. Articles by Delbridge, L. M. Search for Related Content PubMed Articles by Abro, E. Articles by Delbridge, L. M. Social Bookmarking                         What's this?