Brain natriuretic peptide appears to act locally as an antifibrotic factor in the heart

Y. Ogawa, N. Tamura, H. Chusho, K. Nakao

研究成果: Contribution to journalArticle査読

66 被引用数 (Scopus)


In addition to cardiac myocyte hypertrophy, proliferation and increased extracellular matrix production of cardiac fibroblasts occur in response to cardiac overload. This remodeling of the cardiac interstitium is a major determinant of pathologic hypertrophy leading to ventricular dysfunction and heart failure. Atrial and brain natriuretic peptides (ANP and BNP) are cardiac hormones produced primarily by the atrium and ventricle, respectively. Plasma ANP and BNP concentrations are elevated in patients with hypertension, cardiac hypertrophy, and acute myocardial infarction, suggesting their pathophysiologic roles in these disorders. ANP and BNP exhibit diuretic, natriuretic, and vasodilatory activities via a guanylyl cyclase-coupled natriuretic peptide receptor subtype (guanylyl cyclase-A or GC-A). Here we report the generation of mice with targeted disruption of BNP (BNP-/- mice). We observed focal fibrotic lesions in ventricles from BNP-/- mice with a remarkable increase in ventricular mRNA expression of ANP, angiotensin converting enzyme (ACE), transforming growth factor (TGF)-β3, and pro-α1(I) collagen [Col α1(I)], which are implicated in the generation and progression of ventricular fibrosis. Electron microscopic examination revealed supercontraction of sarcomeres and disorganized myofibrils in some ventricular myocytes from BNP-/- mice. No signs of cardiac hypertrophy and systemic hypertension were noted in BNP-/- mice. In response to acute cardiac pressure overload induced by aortic constriction, massive fibrotic lesions were found in all the BNP-/- mice examined, accompanied by further increase of mRNA expression of TGF-β3 and Col α1(I). We postulate that BNP acts as a cardiocyte-derived antifibrotic factor in the ventricle.

ジャーナルCanadian Journal of Physiology and Pharmacology
出版ステータス出版済み - 1 1 2001

All Science Journal Classification (ASJC) codes

  • 生理学
  • 薬理学
  • 生理学(医学)


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