Exercise training combined with angiotensin II receptor blockade limits post-infarct ventricular remodelling in rats.
OBJECTIVE
Our aim was to test the hypothesis that angiotensin II receptor blockade combined with exercise training after myocardial infarction (MI) could attenuate post-MI left ventricular remodelling and preserve cardiac function.


RESULTS
Sprague-Dawley rats underwent ligation of the left descending coronary artery, resulting in MI, or a sham operation. Losartan treatment and exercise training were initiated 1 week after infarction and continued for 8 weeks, either as a single intervention or combined. Collagen volume fraction in the sedentary MI (MISed) group was significantly higher than other MI groups treated with exercise training and/or losartan. Compared with MISed group, hearts of rats receiving exercise and/or losartan treatment had lower tissue inhibitor of matrix metalloproteinase (TIMP) 1. Matrix metalloproteinase (MMP) 2 or MMP-9 did not differ among all groups. Additionally, the level of angiotensin II receptor type 1 (AT1) protein significantly decreased in response to exercise training. Furthermore, angiotensin converting enzyme (ACE) binding was markedly lower in hearts receiving exercise training than in the MISed hearts. Cardiac function was preserved in rats receiving exercise training, and the beneficial effect was further improved by exercise combined with losartan treatment in comparison to the MISed group.


CONCLUSIONS
Our results suggest that post-MI exercise training and/or AngII receptor blockade reduces TIMP-1 expression and mitigates the expressions of ACE and AT1 receptor. These improvements, in turn, attenuate myocardial fibrosis and preserve post-MI cardiac function.
Xu
Xiaohua
X
Laboratory of Cardiovascular Research, University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA.
Wan
Wenhan
W
Ji
Lisa
L
Lao
Shunhua
S
Powers
Anthony S
AS
Zhao
Weiyan
W
Erikson
John M
JM
Zhang
John Q
JQ
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D005081:Exercise Therapy; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; D019808:Losartan