論文 - 北村 和雄
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Plasma adrenomedullin in cerebrovascular disease: a possible indicator of endothelial injury 査読あり
K Kuwasako 1, O Kida, K Kitamura, J Kato, T Eto
Int Angiol 16 ( 4 ) 272 - 279 1997年12月
掲載種別：研究論文（学術雑誌）
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Kuwasako K., Kitamura K., Ishiyama Y., Washimine H., Kato J., Kangawa K., Eto T.
FEBS Letters 414 ( 1 ) 105 - 110 1997年9月
掲載種別：研究論文（学術雑誌） 出版者・発行元：FEBS Letters
Proadrenomedullin N-terminal 20 peptide (PAMP-20) is a potent hypotensive peptide processed from the adrenomedullin (AM) precursor. We developed a specific radioimmunoassay which recognizes the C-terminal region of PAMP-20. Using this radioimmunoassay, the distribution of immunoreactive (ir-) PAMP was determined in porcine tissues. High concentrations of ir-PAMP were observed in the adrenal medulla and in the atrium, and these values were comparable to the corresponding; concentrations of ir-AM. The concentration of ir-PAMP was almost the same as that of ir-AM in the kidney, while ir-PAMP was significantly lower than ir-AM in the ventricle, lung, and aorta. Reversed-phase high performance liquid chromatography in each porcine tissue sample revealed that two major peaks of ir-PAMP existed: one emerged at a position identical to that of authentic porcine PAMP-20; the other unknown peak was eluted earlier. The unknown peptide was purified to homogeneity from porcine adrenal medulla, and its complete amino acid sequence was determined. This peptide was found to be PAMP[9-20] with a C-terminal amide structure, and was named PAMP-12. Intravenous injections of PAMP-12 in anesthetized rats showed a significant hypotensive effect in a dose-dependent fashion, and the effect was comparable to that of PAMP-20. These data indicate that PAMP-12, a major component of ir-PAMP, is processed from the AM precursor, as is PAMP-20, and may participate in cardiovascular control.
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Effect of chronically infused adrenomedullin in two-kidney, one-clip hypertensive rats 査読あり
Khan A.I., Kato J., Ishiyama Y., Kitamura K., Kangawa K., Eto T.
European Journal of Pharmacology 333 ( 2-3 ) 187 - 190 1997年8月
掲載種別：研究論文（学術雑誌） 出版者・発行元：European Journal of Pharmacology
The hypotensive effect of chronically infused adrenomedullin, a potent vasodilator peptide, was examined in conscious two-kidney, one-clip (2K-1C) hypertensive and sham-operated rats. They were infused with 1.0 μg/h of synthetic human adrenomedullin for 14 days by means of osmotic minipumps. Control groups were infused on the same schedule with 0.9% saline. Systolic blood pressure was measured before and during the infusion. Plasma renin activity, aldosterone and human adrenomedullin concentrations were determined at day 14 of the infusion. A significant reduction of systolic blood pressure was observed in the adrenomedullin-infused 2K-1C rats at day 4, and systolic blood pressure remained significantly lower throughout the experiment compared to that of the control 2K-1C. A similar hypotensive effect was seen in the adrenomedullin-infused sham-operated rats. Both the plasma renin activity and aldosterone concentrations of the adrenomedullin-infused 2K-1C and sham groups were significantly reduced compared to those of the respective control, whereas, the plasma human adrenomedullin concentration in the adrenomedullin-infused groups was found to be within the physiological range. These findings demonstrated that chronically infused adrenomedullin had a hypotensive effect accompanied by significant reductions of plasma renin activity and plasma aldosterone concentration in 2K-1C hypertensive and sham-operated rats.
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Nagata N., Kitamura K., Kato J., Naruo H., Eto T., Takasaki M.
Anesthesia and Analgesia 84 ( 6 ) 1193 - 1197 1997年6月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Anesthesia and Analgesia
Cardiopulmonary bypass (CPB) can evoke a systemic inflammatory response, which is accompanied by an increase in plasma cytokines that may stimulate the production of adrenomedullin (AM), a potent vasodilator peptide. This study was undertaken to investigate whether CPB influenced plasma AM concentration in 10 patients undergoing cardiac surgical procedures. We found that the plasma AM concentration increased significantly after the commencement of CPB, with the greatest increase observed at weaning from bypass(P < 0.01). After CPB, plasma AM concentration declined but still exceeded baseline significantly 24 h postoperatively. The increase in the plasma AM concentration at weaning from CPB correlated significantly with aortic cross-clamp time (r = 0.74, P < 0.05). The authors conclude that the secretion of AM into circulation is augmented by CPB in patients undergoing cardiac surgery, which suggests a possible role of AM in cardiovascular regulation during and after surgery with CPB.
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Yoshibayashi M., Kamiya T., Kitamura K., Saito Y., Kangawa K., Nishikimi T., Matsuoka H., Eto T., Matsuo H.
American Journal of Cardiology 79 ( 11 ) 1556 - 1558 1997年6月
掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Cardiology
To elucidate the pathophysiologic significance of adrenomedullin in pulmonary hypertension, we measured plasma adrenomedullin-like immunoreactivity (AM-LI) concentrations in blood samples obtained from various sites during cardiac catheterization by using radioimmunoassay in patients with pulmonary hypertension in comparison with patients without pulmonary hypertension. In patients with pulmonary hypertension, plasma AM- LI concentrations were significantly elevated and there was a significant uptake of AM-LI in pulmonary circulation, indicating the involvement of adrenomedullin in the cardiovascular regulation of pulmonary circulation in pulmonary hypertension.
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Nishio K., Akai Y., Murao Y., Doi N., Ueda S., Tabuse H., Miyamoto S., Dohi K., Minamino N., Shoji H., Kitamura K., Kangawa K., Matsuo H.
Critical Care Medicine 25 ( 6 ) 953 - 957 1997年6月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Critical Care Medicine
Objective: To investigate plasma concentrations of adrenomedullin in patients with septic shock and the potential association of these concentrations with relaxation of vascular tone. Design: Prospective, case series. Setting: Department of Emergency and Critical Care Medicine, Nara Medical University. Patients: Twelve patients who fulfilled the clinical criteria for severe sepals or septic shock (as defined by the Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee) and 13 healthy volunteers. Interventions: Arterial blood samples were obtained via a 20-gauge cannula inserted into each patient's radial artery. Measurements and Main Results: After extraction and purification, plasma adrenomedullin was measured by radioimmunoassay. Systemic vascular resistance index, pulmonary vascular resistance, cardiac index, and stroke volume index were determined with a thermodilution catheter. The mean plasma concentration of adrenomedullin was markedly higher in patients than in controls (226.1 ± 66.4 [SEM] va. 5.05 ± 0.21 fmol/mL, p < .01). Moreover, these concentrations correlated significantly with cardiac index, stroke volume index, and heart rate values, and correlated significantly with decreases in diastolic blood pressure, systemic vascular resistance index, and pulmonary vascular resistance index values. Conclusions: Enhanced production of adrenomedullin in patients with septic shock may contribute to reduced vascular tone, hypotension, or both. More data are needed to clarify the role of adrenomedullin in the regulation of vascular tone in this patient population.
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Changes in cardiac adrenomedullin concentration in renovascular hypertensive rats 査読あり
Ishiyama Y., Kitamura K., Kato J., Sakata J., Kangawa K., Eto T.
Hypertension Research 20 ( 2 ) 113 - 117 1997年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Hypertension Research
We assessed changes in tissue and plasma adrenomedullin levels in two-kidney, one-clip renovascular hypertensive rats. Four weeks after clipping, adrenomedullin concentrations were significantly higher in the cardiac ventricles and lower in the left atrium than the respective values in sham-operated rats. The left ventricular adrenomedullin concentration significantly correlated with systolic blood pressure and the degree of cardiac hypertrophy. No difference was noted in the adrenomedullin concentrations of the adrenal gland, aorta, lung, kidneys, or plasma between the two groups. These findings indicate possible involvement of cardiac adrenomedullin in this model of hypertension.
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Nishikimi T., Morimoto A., Ishikawa K., Saito Y., Kangawa K., Matsuo H., Kitamura K., Takishita S., Matsuoka H.
Clinical and Experimental Hypertension 19 ( 4 ) 503 - 518 1997年5月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical and Experimental Hypertension
The purpose of this study was to investigate the effect of exercise on plasma concentrations of adrenomedullin, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in patients with essential hypertension (n = 15) and in normotensive controls (n = 10). Exercise consisted of two fixed workloads, 40 and 80 watts of work load using a supine bicycle ergometer. Plasma levels of all three peptides at rest were significantly higher in hypertensives than in controls. Plasma concentrations of ANP increased with exercise in both groups and had greater increments in hypertensive patients than in normotensives. Plasma concentrations of BNP increased only in patients with hypertension and the levels of increase correlated with basal plasma BNP levels (r = 0.94, p < 0.001) and with left ventricular mass (r = 0.62, p < 0.01) determined by echocardiography. In contrast, plasma adrenomedullin did not change with exercise in either group. These results suggest that secretion patterns of these peptides are regulated by different mechanisms and that the amount and kind of peptides mobilized by exercise may depend on the underlying diseases or pathophysiologic condition.
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Production of adrenomedullin in human vascular endothelial cells 査読あり
Ishihara T., Kato J., Kitamura K., Katoh F., Fujimoto S., Kangawa K., Tanenao E.
Life Sciences 60 ( 20 ) 1763 - 1769 1997年4月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Life Sciences
To examine the production of adrenomedullin (AM) in human vascular endothelial cells, AM concentration in cultured endothelial cells derived from the human umbilical vein and the conditioned media of the cells were measured in the present study. The cultured endothelial cells secreted immunoreactive AM (ir-AM) into the medium at a rate of 14.7 ± 3.0 fmol/106 cells/24 h with an intracellular ir-AM of 5.2 ± 0.8 fmol/106 cells. Analysis by reverse phase high performance-liquid chromatography (HPLC) showed that ir-AM in both the cells and the conditioned medium eluted at the position identical to that of human AM(1-52). Treatment with dexamethasone significantly augmented the secretion of ir-AM from the cells without any effect on the intracellular ir-AM concentration. Northern blot analysis showed not only the presence of the 1.6 kb human AM precursor mRNA in the endothelial cells, but also its increased expression in the dexamethasone-treated cells. Thus, AM was synthesized and secreted by the human endothelial cells of the umbilical vein, and glucocorticoid augmented the AM production. These findings suggest not only the role of AM as a local modulator of the vascular tone but also the possibility that endothelial cells contribute to circulating AM in the human blood.
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Nishikimi T., Nagata S., Sasaki T., Tomimoto S., Matsuoka H., Takishita S., Kitamura K., Miyata A., Matsuo H., Kangawa K.
Heart 78 ( 4 ) 390 - 395 1997年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Heart
Objective - To examine the pathophysiological significance of adrenomedullin in the pulmonary circulation by investigating the relation between plasma concentrations of adrenomedullin and central haemodynamics in patients with mitral stenosis. Methods - Plasma concentrations of adrenomedullin in blood samples obtained from the femoral veins pulmonary artery, left atrium, and aorta were measured by a newly developed specific radio-immunoassay in 23 consecutive patients with mitral stenosis (16 females and seven males, aged 55 (10) years (mean (SD)) who were undergoing percutaneous mitral commissurotomy. Results - Patients with mitral stenosis had higher concentrations of adrenomedullin than age matched normal controls (3.9 (0.3) v 2.5 (0.3) pmol/l, p < 0.001). There was a reduction in adrenomedullin concentrations between the pulmonary artery and the left atrium (3.8 (0.2) v 3.2 (0.4) pmol/l, p < 0.001). The venous concentrations of adrenomedullin correlated with mean pulmonary artery pressure (r = 0.65, p < 0.001), total pulmonary vascular resistance (r = 0.83, p < 0.0001), and pulmonary vascular resistance (r = 0.65, p < 0.001). Plasma concentrations of adrenomedullin did not change immediately after percutaneous mitral commissurotomy; however, they decreased significantly one week later. Conclusions - Plasma concentrations of adrenomedullin are increased in patients with mitral stenosis. This may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis.
DOI： 10.1136/hrt.78.4.390
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アドレノメデュリン(AM)の多彩な作用 査読あり
北村和雄
医学のあゆみ 182 ( 2 ) 136 - 137 1997年
掲載種別：研究論文（学術雑誌）
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Adrenomedullin動態と脳血管障害 査読あり
竹下啓、高本俊介、小松本悟、奈良昌治、北村和雄
脳卒中 19 ( 6 ) 548 - 548 1997年
掲載種別：研究論文（学術雑誌）
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心血管系でのアドレノメデュリンとPAMP 査読あり
北村和雄、加藤丈司、鶴田敏博、寒川賢治、江藤胤尚
日本内分泌学会雑誌 73 ( 5 ) 330 - 330 1997年
掲載種別：研究論文（学術雑誌）
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新しい循環調節ペプチド"アドレノメデュリン"と"PAMP"の発見とその基礎的・臨床的研究 査読あり
北村和雄
日本内分泌学会雑誌 73 ( 2 ) 63 - 63 1997年
担当区分：筆頭著者 掲載種別：研究論文（学術雑誌）
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アドレノメデュリン 査読あり
北村和雄
心臓 29 ( 4 ) 281 - 289 1997年
担当区分：筆頭著者 掲載種別：研究論文（学術雑誌）
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アドレノメデュリンとPAMP 査読あり
北村和雄、江藤胤尚
日本臨牀 55 ( 8 ) 1963 - 1970 1997年
担当区分：筆頭著者 掲載種別：研究論文（学術雑誌）
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起立性低血圧を認める糖尿病性神経障害患者と健常者におけるティルティング負荷に対する血中アドレノメデュリン(AM)動態 査読あり
中村
日本内分泌学会雑誌 73 ( 2 ) 280 - 280 1997年
掲載種別：研究論文（学術雑誌）
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覚醒ラットにおけるアドレノメデュンの末梢および中枢作用について 査読あり
斉田光彦、下川歩、國武孝人、加藤和男、白阪哲朗、北村和雄、江藤胤尚、河南洋
日本内分泌学会雑誌 73 ( 5 ) 355 - 355 1997年
掲載種別：研究論文（学術雑誌）
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アドレノメデュリン 査読あり
杉田江里、谷山松雄、伴良雄、北村和雄
病理と臨床 15 ( 3 ) 253 - 258 1997年
掲載種別：研究論文（学術雑誌）
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本態性高血圧症に対する塩酸ベニジピン(コニール(R))長期投与の検討-宮崎コニール研究会- 査読あり
江藤胤尚、木田修、北村和雄、児玉健二、近藤宏一、比嘉利信、熊谷治士、田口利文、市来能成、石山雄一郎
臨牀と研究 78 ( 8 ) 2079 - 2086 1997年
掲載種別：研究論文（学術雑誌）