論文 - 北村 和雄
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ヒト冠動脈の培養内皮および平骨筋細胞に発現している動脈硬化促進因子とアドレノメデュリンに対するC反応性蛋白の効果 査読あり
名越康子、桑迫健二、曹袁寧、北村和雄、今村卓郎、江藤胤尚
臨床高血圧 10 ( 2 ) 136 - 137 2004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と関連ペプチドの基礎研究と臨床応用の可能性 査読あり
北村和雄、江藤胤尚
日本内分泌学会雑誌 80 ( 1 ) 38 - 38 2004年
掲載種別：研究論文（学術雑誌）
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治療抵抗性高血圧に低用量スピロノラクトンが有用である 査読あり
北村和雄
臨床高血圧 10 ( 2 ) 132 - 133 2004年
掲載種別：研究論文（学術雑誌）
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血中DRPは高血圧発症のリスクと関係がある 査読あり
北村和雄
臨床高血圧 10 ( 2 ) 134 - 135 2004年
掲載種別：研究論文（学術雑誌）
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ほ乳類に存在する新たなアドレノメデュリン：強力な心血管・腎の調節因子 査読あり
北村和雄
臨床高血圧 10 ( 2 ) 130 - 131 2004年
掲載種別：研究論文（学術雑誌）
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基礎研究の進展 アドレノメデュリンとPAMPの測定法 査読あり
北村和雄
日本臨牀 62 ( 9 ) 216 - 219219 2004年
掲載種別：研究論文（学術雑誌）
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基礎研究の進展 PAMP : アドレノメデュリン前駆体より生合成される新しい降圧ペプチド 査読あり
北村和雄
日本臨牀 62 ( 9 ) 203 - 206206 2004年
掲載種別：研究論文（学術雑誌）
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基礎研究の進展 アドレノメデュリンの構造, 遺伝子, 生合成 査読あり
北村和雄
日本臨牀 62 ( 9 ) 184 - 188 2004年
掲載種別：研究論文（学術雑誌）
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高血圧性臓器障害に関する基礎研究 アドレノメデュリン 査読あり
北村和雄、江藤胤尚
日本臨牀 62 ( 3 ) 239 - 242 2004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は線維芽細胞の活性化とTransforming Growth Factor-β1の発現を抑制することにより冠動脈マトリックスリモデリングを抑制する 査読あり
鶴田敏博、畠山金太、増山浩幸、加藤丈司、今村卓郎、北村和雄、浅田裕士郎、江藤胤尚
日本内分泌学会雑誌 80 ( 2 ) 493 - 493 2004年
掲載種別：研究論文（学術雑誌）
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特論 アドレノメデュリンの心筋梗塞後リモデリングへの臨床応用 査読あり
中村亮斉、加藤丈司、北村和雄、今村卓郎、江藤胤尚
日本臨牀 62 ( 9 ) 302 - 306 2004年
掲載種別：研究論文（学術雑誌）
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Human Adrenomedullin(hAM)およびHuman Proadrenomedullin N-termimal 20 peptide(hPAMP)の超高感度測定法の関発と臨床応用 査読あり
橋田誠一、北村和雄、森下和広、江藤胤尚、
日本内分泌学会雑誌 80 ( 1 ) 197 - 197 2004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の臨床的意義と新たな研究展開 査読あり
加藤丈司、北村和雄、江藤胤尚
日本内分泌学会雑誌 80 ( 1 ) 72 - 72 2004年
掲載種別：研究論文（学術雑誌）
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Increased plasma and joint tissue adrenomedullin concentrations in patients with rheumatoid arthritis compared to those with osteoarthritis 査読あり
Chosa Etsuo,Hamada Hiroaki,北村 和雄,江藤 胤尚,Tajima Naoya
J Rheumatol 30 2553 - 2556 2003年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Kita T., Kitamura K., Hashida S., Morishita K., Eto T.
Hypertension Research 26 ( 11 ) 887 - 893 2003年11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
Arterial stiffness as measured by pulse wave velocity (PWV) is a major predictor of cardiovascular disease. Adrenomedullin (AM), a hypotensive peptide, works as a compensatory factor for arterial sclerosis. The aim of this study was to investigate the relationship between PWV and the plasma concentration of AM in risk-loading patients. One hundred and twenty-six inpatients aged 30 to 75 years with or without varying degrees of atherosclerosis were investigated. Patients with heart and/or renal failure were excluded. The PWV was measured using an automatic waveform analyzer, and the plasma AM level was measured using a newly developed, hypersensitive immunoenzymometric assay system. The PWV increased with the increasing number of cardiovascular risk factors and organ damage in the patients. A positive correlation between the PWV and AM level was observed (r=0.375, p<0.0001, n=126). Seventy-four patients were receiving antihypertensive medications; medication did not affect the correlation. Multivariate regression analysis revealed that the PWV was significantly and independently associated with age, systolic blood pressure, and AM level. These results indicate that the plasma AM concentration could serve as a marker of advanced arterial sclerosis as estimated by increased PWV.
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Cao Y.N., Kitamura K., Kato J., Kuwasako K., Ito K., Onitsuka H., Nagoshi Y., Uemura T., Kita T., Eto T.
Hypertension 42 ( 3 ) 369 - 372 2003年9月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Hypertension
The vasodilator peptide adrenomedullin (AM) elicits diuresis and natriuresis and inhibits aldosterone secretion. The aim of this study was to better understand the role of AM in maintaining water and electrolyte balance during chronic salt loading. Male Wistar rats were divided into a high salt (HS) group that received a diet containing 8% sodium chloride (NaCl) and a normal salt group that received a diet containing 0.4% NaCl. Plasma AM concentrations as well as expression of AM mRNA in the adrenal gland and kidney were then measured after 3, 7, 14, and 28 days. After 28 days, sodium and water excretion were significantly higher in HS rats than in control, although blood pressure and fluid volume were not significantly affected. Moreover, although plasma AM remained unchanged for up to 14 days, it was increased 2.5-fold in HS rats after 28 days on a high salt diet, and there were corresponding 3-fold and 1.5-fold increases in the levels of AM mRNA in the adrenal gland and kidney, respectively. At the same time, expression of calcitonin receptor-like receptor mRNA was significantly upregulated in both kidney and adrenal gland, as was expression of receptor activity-modify protein 1 (RAMP1) and RAMP2 mRNA in the adrenals and expression of RAMP3 in kidneys. Taken together, these results suggest that AM plays a role in the regulation of water and electrolyte balance in animals chronically ingesting high levels of salt.
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Angiotensin II modulates gene expression of adrenomedullin receptor components in rat cardiomyocytes 査読あり
Mishima K., Kato J., Kuwasako K., Imamura T., Kitamura K., Eto T.
Life Sciences 73 ( 13 ) 1629 - 1635 2003年8月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Life Sciences
Both adrenomedullin (AM) and angiotensin II (Ang II) are locally-acting hormones in the cardiac ventricles. Previously we reported that AM inhibits Ang II-induced hypertrophy of cultured rat neonatal cardiomyocytes. In this study, we examined whether Ang II affects the gene expression of the AM receptor components of calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein (RAMP) in rat cardiomyocytes. The mRNA levels of RAMP1 and RAMP3 were significantly elevated following 24-h treatment with Ang II without a change of those of RAMP2 and CRLR. AM increased the intracellular cAMP level and the cAMP accumulation by AM was significantly amplified by the 24-h preincubation with Ang II. The effects of Ang II on RAMP1 and RAMP3 expression were abolished by an Ang II type 1 (AT1) receptor antagonist, but not by an AT2 receptor antagonist. Thus, Ang II modulates gene expression of the AM receptor components via AT1 receptor, suggesting alteration of AM actions by Ang II in cultured rat cardiomyocytes. © 2003 Elsevier Science Inc. All rights reserved.
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Kuwasako K., Kitamura K., Nagoshi Y., Cao Y.N., Eto T.
Journal of Biological Chemistry 278 ( 25 ) 22623 - 22630 2003年6月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Biological Chemistry
When co-expressed with receptor activity-modifying protein (RAMP) 1, calcitonin receptor-like receptor (CRLR) can function as a receptor for both calcitonin gene-related peptide (CGRP) and adrenomedullin (AM). To investigate the structural determinants of ligand binding specificity, we examined the extracellular domain of human (h) RAMP1 using various deletion mutants. Co-expression of the hRAMP1 mutants with hCRLR in HEK-293 cells revealed that deletion of residues 91-94, 96-100, or 101-103 blocked [125I]CGRP binding and completely abolished intracellular cAMP accumulation normally elicited by CGRP or AM. On the other hand, the deletion of residues 78-80 or 88-90 significantly attenuated only AM-evoked responses. In all of these cases, the receptor heterodimers were fully expressed at the cell surface. Substituting alanine for residues 91-103 one at a time had little effect on CGRP-induced responses, indicating that although this segment is essential for high affinity agonist binding to the receptors, none of the residues directly interacts with either CGRP or AM. This finding suggests that RAMPs probably determine ligand specificity by contributing to the structure of the ligand-binding pocket or by allosteric modulation of the conformation of the receptor. Interestingly, the L94A mutant up-regulated surface expression of the receptor heterodimer to a greater degree than wild-type hRAMP1, thereby increasing CGRP binding and signaling. L94A also significantly increased cell surface expression of the hRAMP1 deletion mutant D101-103 when co-transfected with hCRLR, and expression of a L94A/D101-103 double mutant markedly attenuated the activity of endogenous RAMP1 in HEK-293T cells.
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Glycine-extended adrenomedullin exerts vasodilator effect through amidation in the rat aorta 査読あり
Cao Y.N., Kitamura K., Ito K., Kato J., Hashida S., Morishita K., Eto T.
Regulatory Peptides 113 ( 1-3 ) 109 - 114 2003年5月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Regulatory Peptides
Human adrenomedullin (hAM) is an endogenous peptide that has potent vasodilator activity. Mature AM is biosynthesized from its intermediate form, glycine-extended AM (AM-gly), by carboxy-terminal amidation. AM-gly is generally considered to be biologically inactive but is a major molecular form in human and rat plasma. The present study demonstrated that recombinant human AM-gly (hAM-gly) elicits potent vasodilator effect on isolated rat aorta. In aortic rings, hAM-gly produced dose-dependent (0.1-100 nM) relaxation in phenylephrine-precontracted strips (pD2 8.4±0.5). The vasorelaxant potency of hAM-gly was comparable to that of hAM (pD2 8.6±0.2) but hAM-gly took a significantly (P<0.01) longer time to reach the maximal relaxation compared with hAM (Tmax 23±4 vs. 5±2 min). Vasorelaxant responses to hAM-gly were abolished by endothelial removal. Nω-nitro-L-arginine (L-NNA) and AM(22-52) significantly (P<0.01) reduced the vasodilator effect of hAM-gly. Furthermore, 4-phenyl-3-butenoic acid (PBA), an alpha-amidation enzyme inhibitor, significantly (P<0.05) inhibited the vasorelaxant responses to hAM-gly without any effect on the hAM-induced relaxation, suggesting the possible process of amidation in the rat aorta. We further clarified that the aorta has the ability to convert exogenous hAM-gly to mature hAM and the conversion is inhibited by PBA. These results suggest that the circulating AM-gly may play a role in regulating vascular tone and increased plasma AM-gly may be involved in the pathophysiology of cardiovascular diseases. © 2003 Elsevier Science B.V. All rights reserved.
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Two cases of pheochromocytoma associated with tetralogy of fallot 査読あり
Kita T., Imamura T., Date H., Kitamura K., Moriguchi S., Sato Y., Asada Y., Eto T.
Hypertension Research 26 ( 5 ) 433 - 437 2003年5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 report two cases of pheochromocytoma combined with tetralogy of Fallot who showed different clinical courses. Case 1 was a 45-year-old woman with a history of radical operation for tetralogy of Fallot at 20 years of age. She presented with sudden hypertensive attack, and was diagnosed with pheochromocytoma of the left adrenal gland. She was treated surgically, and her high plasma noradrenaline level normalized. Case 2 was a 41-year-old woman who had been suffering from severe cyanosis due to tetralogy of Fallot throughout her life. A palliative operation had been performed at 7 years of age, but a radical operation had not been performed. She has had resistant hypertension since 38 years of age. She was diagnosed as having pheochromocytoma of the left adrenal gland at 41 years of age, but surgery was not performed. She was pharmacologically treated with doxazosin, followed by bisoprolol. Her symptoms somewhat improved, although she continued to have high plasma levels of noradrenaline and adrenomedullin. The combination of pheochromocytoma with tetralogy of Fallot or cyanotic congenital heart disease is rare; however, pheochromocytoma and congenital heart disease might be related through chronic hypoxia and/or gene abnormalities. The presence of pheochromocytoma worsens the hemodynamic state in patients with congenital heart disease regardless of whether radical surgery for congenital heart disease had been performed. Differential diagnosis of pheochromocytoma could be paramount in congenital heart disease patients who show unexpected or unusual symptoms.