Document Detail

The renin-angiotensin system and volume overload-induced cardiac hypertrophy in rats. Effects of angiotensin converting enzyme inhibitor versus angiotensin II receptor blocker.
MedLine Citation:
PMID:  8443912     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The degree of cardiac hypertrophy is not only load dependent: Among other factors, the renin-angiotensin system may play a role in the regulation of cardiac myocyte growth. METHODS AND RESULTS: To evaluate the role of the renin-angiotensin system in volume overload-induced cardiac hypertrophy, we assessed: 1) the time course of changes in cardiac hemodynamics, cardiac anatomy, and plasma and cardiac renin activity in response to volume overload induced by two sizes of abdominal aortocaval shunt and 2) the effects of chronic treatment with an angiotensin converting enzyme inhibitor (ACEI) versus an angiotensin II receptor blocker on hemodynamics and cardiac hypertrophy. Drug treatment started 3 days before shunt surgery. An increase in left ventricular end-diastolic pressure (LVEDP) and the development of right ventricular (RV) and left ventricular (LV) eccentric hypertrophy in response to volume overload occurred within the first week after induction of the shunt. Plasma renin activity (PRA) and cardiac renin activity peaked shortly after induction of the shunt. During the chronic phase, LVEDP and PRA decreased somewhat but remained significantly elevated up to 7 weeks after shunt surgery. Cardiac renin activity returned toward normal within 4 weeks after surgery. Treatment with the ACEI enalapril caused only a modest decrease in LV internal diameter but did not affect increases in LV and RV weights in response to volume overload despite a major decrease in LVEDP after chronic treatment. In contrast, treatment with the angiotensin II receptor blocker losartan, which had similar effects on cardiac and peripheral hemodynamics, prevented dilation of the LV after 7 days and attenuated the dilation of the LV after 28 days. Moreover, increases in LV and RV weights were significantly attenuated by losartan. CONCLUSIONS: The development of volume overload-induced cardiac hypertrophy is associated with significant increases in PRA and cardiac renin activity shortly after induction of an aortocaval shunt. Whereas the two blockers of the renin-angiotensin system decreased LVEDP to a similar extent, only the angiotensin II receptor blocker blunted the hypertrophic response of the heart to volume overload, which is indicative for other than hemodynamic determinants of the cardiac hypertrophic response. One trophic factor may be cardiac angiotensin II generated via an angiotensin II-forming enzyme resistant to ACEI and possibly activated by cardiac volume overload.
M Ruzicka; B Yuan; E Harmsen; F H Leenen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  87     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1993 Mar 
Date Detail:
Created Date:  1993-04-06     Completed Date:  1993-04-06     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  921-30     Citation Subset:  AIM; IM    
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
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MeSH Terms
Angiotensin II / antagonists & inhibitors
Aorta / surgery
Arteriovenous Shunt, Surgical
Biphenyl Compounds / pharmacology
Body Weight / drug effects
Cardiac Volume* / drug effects
Cardiomegaly / etiology,  metabolism,  physiopathology*
Enalapril / pharmacology
Hemodynamics / drug effects
Imidazoles / pharmacology
Myocardium / metabolism,  pathology
Organ Size / drug effects
Rats, Wistar
Renin / blood,  metabolism
Renin-Angiotensin System*
Tetrazoles / pharmacology
Venae Cavae / surgery
Reg. No./Substance:
0/Biphenyl Compounds; 0/Imidazoles; 0/Tetrazoles; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 75847-73-3/Enalapril; EC

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