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(Circulation. 1995;92:1558-1564.)
© 1995 American Heart Association, Inc.
Articles |
Rapid Ventricular Induction of Brain Natriuretic Peptide Gene Expression in Experimental Acute Myocardial Infarction
From the Second Division, Department of Medicine (N.H., H.I., O.N., S.S., Y.O., I.M., T.Y., K. Nakao) and Department of Anesthesia (G.S.), Kyoto University School of Medicine; the Department of Pharmacy (Y.H., M.Y., R.H.), Kyoto University Hospital; the Department of Pathology (K. Nakanishi), National Defense Medical College; and the Division of Cardiology (H.Y.), Kumamoto University School of Medicine, Japan.
Correspondence to Kazuwa Nakao, MD, PhD, Second Division, Department of Medicine, Kyoto University School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan.
Background We have demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone predominantly synthesized in and secreted from the ventricle. We have also reported that, compared with atrial natriuretic peptide (ANP), the plasma concentration of BNP is increased to a greater degree in patients with congestive heart failure and more rapidly in patients with acute myocardial infarction (AMI).
Methods and Results To investigate ventricular gene expression of BNP in AMI, we analyzed plasma and ventricular BNP concentrations along with ventricular BNP mRNA in rats with AMI produced by coronary artery ligation. The BNP concentration in the left ventricle increased about 2-fold as early as 12 hours postinfarction and 5-fold 1 day postinfarction compared with sham-operated rats, whereas left ventricular ANP concentration remained unchanged within 1 day. The tissue concentration of BNP increased in the noninfarcted region as well as in the infarcted region. The surviving myocytes in and around the necrotic tissues in the infarcted region were intensely stained with the anti-BNP antiserum, indicating augmented production in the remaining myocytes in the infarcts. The BNP concentration in the right ventricle also increased about 10-fold 12 hours postinfarction, whereas the ANP concentration remained unchanged within 12 hours. Northern blot analysis revealed that BNP mRNA expression was augmented 3-fold in the left ventricle as early as 4 hours postinfarction. In contrast, ANP mRNA expression was unchanged. Reflecting the rapid induction of ventricular BNP production, the plasma BNP concentration rose to about 100 pg/mL 12 hours postinfarction (sham-operated rats, <70 pg/mL).
Conclusions These results demonstrate the rapid induction of ventricular BNP gene expression in rats with AMI compared with ANP and suggest that BNP gene expression in the ventricle is regulated distinctively from ANP gene expression against acute ventricular overload. They also suggest that the BNP gene can be one of the acutely responsive cardiac genes for the ventricular overload and suggest a possible pathophysiological role of BNP distinct from ANP in AMI.
Key Words: natriuretic peptides • myocardial infarction
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M. Harada, H. Itoh, O. Nakagawa, Y. Ogawa, Y. Miyamoto, K. Kuwahara, E. Ogawa, T. Igaki, J. Yamashita, I. Masuda, et al. Significance of Ventricular Myocytes and Nonmyocytes Interaction During Cardiocyte Hypertrophy : Evidence for Endothelin-1 as a Paracrine Hypertrophic Factor From Cardiac Nonmyocytes Circulation, November 18, 1997; 96(10): 3737 - 3744. [Abstract] [Full Text]
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T. Tsutamoto, A. Wada, K. Maeda, T. Hisanaga, Y. Maeda, D. Fukai, M. Ohnishi, Y. Sugimoto, and M. Kinoshita Attenuation of Compensation of Endogenous Cardiac Natriuretic Peptide System in Chronic Heart Failure : Prognostic Role of Plasma Brain Natriuretic Peptide Concentration in Patients With Chronic Symptomatic Left Ventricular Dysfunction Circulation, July 15, 1997; 96(2): 509 - 516. [Abstract] [Full Text]
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L. Eklund, J. Piuhola, J. Komulainen, R. Sormunen, C. Ongvarrasopone, R. Fassler, A. Muona, M. Ilves, H. Ruskoaho, T. E. S. Takala, et al. Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice PNAS, January 30, 2001; 98(3): 1194 - 1199. [Abstract] [Full Text] [PDF]
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