| Project/Area Number |
61570405
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HIRATA Yasunobu University of Tokyo, 医学部(病), 助手 (70167609)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Masao University of Tokyo, 医学部, 教授 (90010363)
MATSUOKA Hiroaki University of Tokyo, 医学部, 講師 (20111544)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1988: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1987: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | atrial natriuretic peptide / atrial pressure / urinary sodium excretion / cyclic GMP / secretion / blood pressure / congestive heart failure / 高血圧 / 心筋症ハムスター / 心室 / ノルエピネフリン / ドーパミン / 心肥大 / ペーシング / 迷走神経切断 / 尿中ナトリウム排泄量 / 血漿濃度 / 体液量 / 浸透圧 / 心房圧尿中ナトリウム排泄量 |
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| Research Abstract |
To explore the pathophysiological roles of atrial natriuretic peptide (ANP), we examined the relationship between atrial pressure and plasma concentration of ANP in various experimental and clinical conditions and the effects of ANP infusion into patients with cardiovascular and renal diseases. Both volume expansion and hyperosmotic stimulus in rats increased plasma concentration of ANP. This increase in the plasma ANP concentration was associated with increases in urinary Na excretion and atrial pressure. Left atrial ballooning and right atrial rapid pacing also increased ANP secretion and atrial pressure. In patients with congestive heart failure, plasma ANP concentration increased with the severity index of the heart failure symptoms, resulting in a significant positive correlation of plasma ANP concentration with atrial pressure. Plasma ANP level was also elevated during paroxysmal atrial tachycardia. These results suggest that atrial strtch seems to be the most important stimulus for ANP secretion. In addition to heart diseases, various kinds of edematous disorders and hypertension also showed increased plasma ANP concentration. When ANP was infused into patients with these diseases, ANP exerted potent vasorelaxant (depressor), natriuretic and alsdosterone suppressive effects, suggesting the possible therapeutic use of this peptide. ANP infusion markedly elevated plasma and urinary cGMP concentrations. These findings support that cGMP acts as an intracellular second messenger of ANP. Furthermore, basal plasma cGMP level was also closely correlated with the plasma concentration of ANP. This suggests that plasma cGMP seems to be a good marker of endogenous ANP activity. Thus, ANP, which secretes through direct or indirect atrial extention, may play a pathophysiological role in blood pressure and body fluid volume regulation.
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