Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction

Norio Hama, Hiroshi Itoh, Gotaro Shirakami, Osamu Nakagawa, Shin Ichi Suga, Yoshihiro Ogawa, Izuru Masuda, Kuniaki Nakanishi, Takaaki Yoshimasa, Yukiya Hashimoto, Masayuki Yamaguchi, Ryouhei Hori, Hirofumi Yasue, Kazuwa Nakao

Research output: Contribution to journalArticlepeer-review

390 Citations (Scopus)

Abstract

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 gent 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.

Original languageEnglish
Pages (from-to)1558-1564
Number of pages7
JournalCirculation
Volume92
Issue number6
DOIs
Publication statusPublished - 1995 Sept 15
Externally publishedYes

Keywords

  • myocardial infarction
  • natriuretic peptides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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