Changes in production and metabolism of brain natriuretic peptide in rats with myocardial necrosis.
In this study, we employed rat model of acute myocardial necrosis induced by isoproterenol (ISO) to study the possible roles of corin, the protease uniquely distributing in myocardium to convert pro-brain natriuretic peptide (proBNP) to BNP, and neutral endopeptidase (NEP), the major enzyme to degrade BNP, in changing the levels of BNP. In rats with isoproterenol alone, the myocardium necrosis occurred and the cardiac function was inhibited; the BNP contents in plasma and myocardium were upregulated, so did the myocardial corin mRNA level; the NEP activity in plasma and myocardium were downregulated. Omapatrilat (OMA) treatment relieved myocardial lesions and improved cardiac function. In the plasma and myocardium, omapatrilat treatment increased BNP contents, reduced NEP activity; in myocardium, mRNA level of proBNP and corin decreased, but NEP mRNA expression increased. Our study confirmed that omapatrilat treated myocardial necrosis effectively and suggested that increased BNP in rats with myocardial necrosis could depend on increased production and conversion as well as decreased degradation.
Jiang
Wei
W
Institute of Cardiovascular Diseases, Peking University First Hospital, Beijing, No. 8, Xi Shiku street, Beijing 100034, PR China.
Cai
Da-Yong
DY
Pan
Chun-Shui
CS
Qi
Yong-Fen
YF
Jiang
Hong-Feng
HF
Geng
Bing
B
Tang
Chao-Shu
CS
D000818:Animals; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013841:Thiazepines / Q000494:pharmacology
D011725:Pyridines; D013841:Thiazepines; D020097:Natriuretic Peptide, Brain; C106266:omapatrilat; D007545:Isoproterenol