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J Am Coll Cardiol, 1998; 32:1832-1838
© 1998 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Expression and distribution of brain natriuretic peptide in human right atria

Kiyoshi Doyama, MD*, Manabu Fukumoto, MD*, Genzou Takemura, MD{dagger}, Masaru Tanaka, MD*, Teiji Oda, MD{ddagger}, Koji Hasegawa, MD*, Tsukasa Inada, MD*, Seiji Ohtani, MD*, Takako Fujiwara, MD§, Hiroshi Itoh, MD*, Kazuwa Nakao, MD*, Shigetake Sasayama, MD* and Hisayoshi Fujiwara, MD{dagger}

* Third and Second Department of Internal Medicine and Second Department of Pathology, Kyoto University School of Medicine, Kyoto, Japan
{dagger} Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan
{ddagger} Department of Cardiovascular Surgery, Rakuwakai-Otowa Hospital, Kyoto, Japan
§ Kyoto Women’s University, Kyoto, Japan

Manuscript received March 16, 1998; revised manuscript received July 20, 1998, accepted August 20, 1998.

Address for correspondence: Dr. Hisayoshi Fujiwara, Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu 500-8705, Japan
gifuim-gif{at}umin.u-tokyo.ac.jp

Objectives. We investigated expression of brain natriuretic peptide (BNP) as well as atrial natriuretic peptide (ANP) and their genes in human right atria. Their relations with atrial pressure were also examined.

Background. The BNP plays a roll in electrolyte-fluid homeostasis such as ANP. The tissue level is reported to be elevated in the failing ventricles. However, expression and transmural distribution of BNP in the atria remain unclear.

Methods. Expression of ANP and BNP was immunohistochemically investigated in the right atrial (RA) specimens from 21 patients who had undergone cardiac surgery. The mRNA of specimens were quantitatively measured by Northern blot analysis and also evaluated by in situ hybridization. In addition, plasma levels of ANP and BNP were measured in the patients.

Results. The BNP immunoreactivity was diffusely seen in RA tissue of patients with mean RA pressure (mRAP) of 5 mm Hg or more, but it was noted only in the subendocardial half of the atria of those with mRAP less than 5 mm Hg. There was a significant correlation between the incidence of BNP-positive myocytes and mRAP (r = 0.850, p < 0.0001). Conversely, ANP-positive myocytes were found diffusely in all cases. In Northern blot analysis, the mRNAs levels of ANP and BNP in the atrial tissue were positively correlated with the mRAP (ANP, p = 0.775, p < 0.005 and BNP, p = 0.771, p < 0.005). In situ hybridization confirmed these findings. The mRNA levels were significantly correlated to each other (r = 0.845, p < 0.0002). Plasma ANP and BNP levels were elevated in the patients compared with that in controls; however, none were significantly correlated with the mRAP.

Conclusions. Expression of BNP and BNP mRNA is augmented in the atria with increased pressure, and distributed predominantly in the subendocardial side. The level of BNP mRNA was well correlated with that of ANP mRNA. Thus, these two genes might be commonly regulated in response to atrial pressure.

Abbreviations and Acronyms
  ANP = atrial natriuretic peptide
  BNP = brain natriuretic peptide
  CHF = congestive heart failure
  mRAP = mean right atrial pressure
  NYHA = New York Heart Association
  RA = right atria(l)




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