Document Detail

Effects of angiotensin II type 1 receptor blockade in ApoE-deficient mice with post-ischemic heart failure.
MedLine Citation:
PMID:  12827021     Owner:  NLM     Status:  MEDLINE    
We investigated in mice whether atherosclerosis exacerbates the development of post-ischemic heart failure and alters the beneficial effects of long-term angiotensin II type 1 receptor blockade in this model. ApoE-deficient (ApoE(-/-)) and C57BL/6J (C57) mice with myocardial infarction (coronary ligation) received vehicle (C57 and ApoE(-/-)) or irbesartan (Ir, 50mg/kg/d orally, C57-Ir and ApoE(-/-)-Ir). Ten months post myocardial infarction, survival rates were similar in C57 (58%) and ApoE(62%). Atherosclerosis induced no significant alteration in blood pressure, cardiac output (fluospheres), total peripheral resistance, or shortening fraction (echocardiography) but increased renal resistance (+50%, P<0.05). Chronic Ir treatment significantly improved survival to a similar extent in both C57-Ir (85%) and ApoE(-/-)-Ir (86%). It also decreased blood pressure to a similar extent in both strains (-16% and -18%, both P<0.05). In C57-Ir mice, Ir did not modify cardiac output or total peripheral resistance, but it decreased renal resistance (-28%, P<0.001) and left-ventricular weight (-28%, P<0.05). In ApoE(-/-)-Ir mice, Ir limited atherosclerotic lesions (-13%, P<0.05), increased cardiac output (+28%, P<0.05) and shortening fraction (+24%, P<0.05), and decreased total peripheral resistance (-33%, P<0.01), renal resistance (-61%, P<0.001), and left-ventricular weight (-27%, P<0.001). In conclusion, atherosclerosis does not worsen heart failure development in mice and, although the beneficial cardiovascular effects of AT1 receptor blockade are greater in ApoE(-/-) than in C57, reduction in mortality is similar in both strains.
Sandrine Pons; Albert Hagège; Paul Fornes; Marianne Gervais; Jean-François Giudicelli; Christine Richer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  42     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-26     Completed Date:  2003-11-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17-23     Citation Subset:  IM    
Département de Pharmacologie, INSERM E 00-01, Faculté de Médecine, La Kremlin-Bicêtre, France.
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MeSH Terms
Angiotensin II Type 1 Receptor Blockers*
Apolipoproteins E / deficiency*
Arteriosclerosis / complications,  metabolism
Biphenyl Compounds / pharmacology,  therapeutic use*
Blood Pressure / drug effects
Cardiac Output / drug effects
Disease Models, Animal
Mice, Inbred C57BL
Mice, Knockout
Myocardial Infarction / drug therapy*,  etiology,  metabolism
Myocardial Ischemia / complications,  metabolism*
Tetrazoles / pharmacology,  therapeutic use*
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Apolipoproteins E; 0/Biphenyl Compounds; 0/Tetrazoles; 138402-11-6/irbesartan

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