Open AccessRegression of cardiac hypertrophy in the SHR by combined renin-angiotensin system blockade and dietary sodium restriction
Author(s) -
Emad Uddin Abro,
Cory D. Griffiths,
Trefor Morgan,
L. Delbridge
Publication year - 2001
Publication title -
jraas. journal of the renin-angiotensin-aldosterone system/journal of the renin-angiotensin-aldosterone system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 46
eISSN - 1752-8976
pISSN - 1470-3203
DOI - 10.1177/14703203010020012601
Subject(s) - medicine , renin–angiotensin system , endocrinology , angiotensin ii , aldosterone , candesartan , blockade , muscle hypertrophy , sodium , ace inhibitor , angiotensin converting enzyme , low sodium diet , angiotensin receptor , chemistry , receptor , blood pressure , organic chemistry
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.