Effect of long-term B-type natriuretic peptide treatment on left ventricular remodeling and function after myocardial infarction in rats.
Although short-term B-type natriuretic peptide (BNP) treatment has been shown to be effective for decompensated congestive heart failure, little is known about the effects of long-term BNP treatment in ventricular remodeling and heart failure in response to myocardial infarction. The aim of the present study was to investigate the effects of long-term BNP treatment on ventricular remodeling and heart failure after myocardial infarction in rats. Myocardial infarction was induced by ligating the left anterior descending coronary artery. The surviving rats were randomly divided into four groups: 1) vehicle-treated myocardial infarction group ('vehicle-treated group'), 2) rats treated with low-dose BNP ('low BNP group'), 3) rats treated with high-dose BNP ('high BNP group'), 4) sham-operated group. Eight weeks after the operation, rats were sacrificed. Compared with the sham-operated group, the vehicle-treated group had significantly higher collagen deposition and angiotensin II levels (P<0.01) and a significantly lower cardiac function (P<0.05). Both BNP-treated groups had significant improvement of these indexes compared with the vehicle-treated group (P<0.01). The high BNP group had significantly less collagen deposition and better cardiac function than the untreated and low BNP groups. Moreover, the mRNA and protein expression of TGFbeta1 and Smad2 in the vehicle-treated group was significantly higher than in the sham-operated group (P<0.01). Both BNP-treated groups had a suppression of TGFbeta1 and Smad2 expression (P<0.01). In conclusion, long-term treatment with BNP prevents ventricular remodeling and deterioration of cardiac function in a dose-dependent fashion, a process that may be associated with the inhibition of TGFbeta1/ Smad2 signaling.
He
Jiangui
J
Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, 510080 Guangzhou, China. hejiangui@163.com
Chen
Yili
Y
Huang
Yiyi
Y
Yao
Fengjuan
F
Wu
Zhongkai
Z
Chen
Shenglong
S
Wang
Lichun
L
Xiao
Pingxi
P
Dai
Gang
G
Meng
Rongsen
R
Zhang
Chengxi
C
Tang
Lilong
L
Huang
Yuli
Y
Li
Zhiming
Z
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D045283:Natriuretic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects*
D045283:Natriuretic Agents; D012333:RNA, Messenger; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D003094:Collagen