Papers - KITAMURA Kazuo
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レニン・アンジオテンシン系の新たなペプチドproangiotensin-12の単離同定と組織濃度の検討 Reviewed
永田さやか、加藤丈司、北村和雄
日本内分泌学会雑誌 83 ( 2 ) 580 - 580 2007
Publishing type：Research paper (scientific journal)
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Nagata S., Kato J., Sasaki K., Minamino N., Eto T., Kitamura K.
Biochemical and Biophysical Research Communications 350 ( 4 ) 1026 - 1031 2006.12
Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
The renin-angiotensin (RA) system plays an important role in regulating blood pressure and fluid balance. In the search for bioactive peptides with an antibody binding to the N-terminal portion of angiotensin II (Ang II), we isolated a new angiotensinogen-derived peptide from the rat small intestine. Consisting of 12 amino acids, this peptide was termed proangiotensin-12 based on its possible role of an Ang II precursor. Proangiotensin-12 constricted aortic strips and, when infused intravenously, raised blood pressure in rats, while both the vasoconstrictor and pressor response to proangiotensin-12 were abolished by captopril and by CV-11974, an Ang II type I receptor blocker. Proangiotensin-12 is abundant in a wide range of organs and tissues including the small intestine, spleen, kidneys, and liver of rats. The identification of proangiotensin-12 suggests a processing cascade of the RA system, different from the cleavage of angiotensinogen to Ang I by renin. © 2006.
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Adrenomedullin And Its Related Peptides Reviewed
Kitamura K., Kato J.
Handbook of Biologically Active Peptides 1163 - 1168 2006.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Handbook of Biologically Active Peptides
Adrenomedullin (AM) is a potent vasodilator peptide that exerts major effects on cardiovascular function. AM, initially isolated from human pheochromocytoma tissue, is biosynthesized in a wide variety of organs and cells. The basic characteristic effect of AM is a potent, long-lasting hypotension that is dose-dependent in several species, including humans. AM dilates resistance vessels in the kidney, brain, lung, hind limbs, and mesentery in animals. In addition to AM, proadrenomedullin N-terminal 20 peptide (PAMP) is found to be processedfrom the AM precursor. Both AM and PAMP show hypotensive effects in anesthetized rats but exhibit different hypotensive mechanisms. Further, AM possesses multiple biological effects closely related to cardiovascular homeostasis. Plasma AM concentration is increased in patients with several cardiovascular diseases such as hypertension, congestive heart failure, renal failure, and septic shock. It has been recognized that AM is one of the important vasoactive peptides involved in the physiology and pathophysiology of circulation and body fluid control. © 2006 Elsevier Inc. All rights reserved.
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Masuyama H., Tsuruda T., Kato J., Imamura T., Asada Y., Stasch J.P., Kitamura K., Eto T.
Hypertension 48 ( 5 ) 972 - 978 2006.11
Publishing type：Research paper (scientific journal) Publisher：Hypertension
It is unknown whether long-term pharmacological stimulation of soluble guanylate cyclase (sGC), elevating intracellular cGMP levels, has a beneficial effect on hypertension. The purpose of this study is to investigate the effects of BAY41-2272, an orally available sGC stimulator, on cardiovascular remodeling in hypertensive rats. Eight-week-old male Wistar rats with hypertension induced by angiotensin II infused subcutaneously at 250 ng/kg per minute were treated orally with a low ([L] 2 mg/kg per day) or high ([H] 10 mg/kg per day) dose of BAY41-2272 for 14 days. BAY41-2272-H partially suppressed the rise in blood pressure and reduced the heart weight (4.20±0.34 versus 3.68±0.20 mg/g; P<0.01), whereas BAY41-2272-L had no effect. However, both doses decreased the angiotensin II-induced left ventricular accumulation of collagen in the perivascular area (L, -20%, P<0.05; H, -30%, P<0.01) and myocardial interstitium (L, -21%, P<0.05; H, -38%, P<0.01), reducing the number of activated fibroblasts surrounding coronary arteries (L, -74%; H, -79%; P<0.05). BAY41-2272 downregulated the angiotensin II-induced left ventricular gene expression of type 1 collagen (L, -41%, P<0.05; H, -49%, P<0.01) and transforming growth factor-β1 (L, -49%, P<0.05; H, -65%, P<0.01). cGMP levels were elevated by BAY41-2272 not only in the left ventricle, but also in cultured cardiac fibroblasts, resulting in reduced thymidine incorporation into the cells. Thus, stimulation of sGC by BAY41-2272 attenuates fibrosis of the left ventricle in rats with angiotensin II-induced hypertension partly in a pressure-independent manner, suggesting an important role for sGC generating cGMP in inhibiting cardiovascular remodeling. © 2006 American Heart Association, Inc.
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Bone and bone related biochemical examinations. Hormone and hormone related substances. Calcitonin gene-related peptide (CGRP) Reviewed
Kenji Kuwasako 1, Kazuo Kitamura
Clin Calcium 16 ( 6 ) 905 - 912 2006.6
Publishing type：Research paper (scientific journal)
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Adrenomedullin in mast cells of abdominal aortic aneurysm Reviewed
Tsuruda T., Kato J., Hatakeyama K., Yamashita A., Nakamura K., Imamura T., Kitamura K., Onitsuka T., Asada Y., Eto T.
Cardiovascular Research 70 ( 1 ) 158 - 164 2006.4
Publishing type：Research paper (scientific journal) Publisher：Cardiovascular Research
Objectives: Produced by vascular walls, adrenomedullin (AM) exerts antifibrotic actions in the process of cardiovascular remodeling. The purpose of this study was to examine the pathophysiological role of AM in the development of human abdominal aortic aneurysm (AAA). Methods and results: Immunohistochemical analyses revealed that vascular smooth muscle cells in the media were positive for AM in the early stage of atherosclerotic aorta. Intense immunoreactivity was observed in mast cells of the outer media and adventitia of AAA, and the number of mast cells was greater (p < 0.01) in AAA than in atherosclerotic aorta without any aneurysmal change. To determine the role of AM in mast cells, we examined cultured human mast cell leukemia line-1 (HMC-1) and fibroblasts isolated from AAA patients. Cultured HMC-1 cells were found to express preproAM gene and release AM peptide into the cultured media. When assessed by collagenase-sensitive [3H]proline incorporation and procollagen type I C-peptide secretion, collagen synthesis in co-culture of HMC-1 and the fibroblasts was reduced by 10- 6 mol/L synthetic AM, while conversely, it increased following blockade of the action of endogenous AM with 10 μg/mL anti-AM monoclonal antibody. Conclusion: The present study suggests an anti-fibrotic role for AM released from mast cells, providing new insight into the biological actions of mast cell-derived AM in the development of AAA. © 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
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レニン・アンジオテンシン系阻害薬を再考する Reviewed
北村和雄
臨床のあゆみ 69 24 - 25 2006.4
Language：Japanese Publishing type：Research paper (scientific journal)
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長期のベニジピン療法により降圧を超えた動脈硬化度の改善が得られる Reviewed
北 俊弘、鈴木良彦、江藤胤尚、北村和雄
Arterial Stiffness 10 48 - 49 2006.4
Language：Japanese Publishing type：Research paper (scientific journal)
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Plasma adrenomedullin level and development of hypertension Reviewed
Kato J, Kitamura K, Eto T
J Hum Hypertens 20 566 - 570 2006.4
Language：English Publishing type：Research paper (scientific journal)
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Increased production of adrenomedullin in glomeruli from anti-glomerular basement membrane (GBM) glomerulonephritis rats treated with methylprednisolone. Reviewed
Iwatsubo S, Fujimoto S, Matsumoto M, Sato Y, Hara S, Kitamura K, Eto T
Nephron Exp Nephrol 104 e41 - e47 2006.4
Language：English Publishing type：Research paper (scientific journal)
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Kuwasako K., Cao Y.N., Chu C.P., Iwatsubo S., Eto T., Kitamura K.
Journal of Biological Chemistry 281 ( 11 ) 7205 - 7213 2006.3
Publishing type：Research paper (scientific journal) Publisher：Journal of Biological Chemistry
Receptor activity-modifying proteins (RAMPs) enable calcitonin receptor-like receptor (CRLR) to function as a calcitonin gene-related peptide receptor (CRLR/RAMP1) or an adrenomedullin (AM) receptor (CRLR/RAMP2 or -3). Here we investigated the functions of the cytoplasmic C-terminal tails (C-tails) of human RAMP1, -2, and -3 (hRAMP1, -2, and -3) by cotransfecting their C-terminal deletion or progressive truncation mutants into HEK293 cells stably expressing hCRLR. Deletion of the C-tail from hRAMP1 had little effect on the surface expression, function, or intracellular trafficking of the mutant heterodimers. By contrast, deletion of the C-tail from hRAMP2 disrupted transport of hCRLR to the cell surface, resulting in significant reductions in 125I-hAM binding and evoked cAMP accumulation. The transfection efficiency for the hRAMP2 mutant was comparable with that for wild-type hRAMP2; moreover, immunocytochemical analysis showed that the mutant hRAMP2 remained within the endoplasmic reticulum. FACS analysis revealed that deleting the C-tail from hRAMP3 markedly enhances AM-evoked internalization of the mutant heterodimers, although there was no change in agonist affinity. Truncating the C-tails by removing the six C-terminal amino acids of hRAMP2 and -3 or exchanging their C-tails with one another had no effect on surface expression, agonist affinity, or internalization of hCRLR, which suggests that the highly conserved Ser-Lys sequence within hRAMP C-tails is involved in cellular trafficking of the two AM receptors. Notably, deleting the respective C-tails from hRAMPs had no effect on lysosomal sorting of hCRLR. Thus, the respective C-tails of hRAMP2 and -3 differentially affect hCRLR surface delivery and internalization. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
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テルミサルタンが、あらゆる臓器障害に先行して起こる血管内皮機能障害の指標であるNOを増加させたことは、きわめて意義深い Reviewed
北村和雄
Medical Tribune 2006.2
Language：Japanese Publishing type：Research paper (scientific journal)
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第14回(最終回) アドレノメデュリン Reviewed
加藤丈司、北村和雄、江藤胤尚
血圧 13 ( 2 ) 225 - 227 2006
Publishing type：Research paper (scientific journal)
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PAMP単独過剰発現ラットの開発とPAMPの血管新生作用 Reviewed
北村和雄、Yuan-NingCao、江藤胤尚
日本内分泌学会雑誌 82 ( 1 ) 116 - 116 2006
Publishing type：Research paper (scientific journal)
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アドレノメデュリン Reviewed
北村和雄
日本臨牀 64 ( 2 ) 217 - 221 2006
Publishing type：Research paper (scientific journal)
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降圧因子としてのアドレノメデュリンとPAMP Reviewed
北村和雄
循環制御 27 ( 4 ) 312 - 316 2006
Publishing type：Research paper (scientific journal)
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糖尿病患者の心血管発症イベントの抑制を目指して:BNPとCRPのイベント発症予測因子としての有用性 Reviewed
鶴田敏博、加藤丈司、隅専浩、三嶋和也、今村卓郎、北村和雄、江藤胤尚
日本内分泌学会雑誌 82 ( 2 ) 506 - 506 2006
Publishing type：Research paper (scientific journal)
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閉塞性動脈血栓の形成における5-HT2A受容体の関与‐家兎動脈硬化性血栓モデルでの検討 Reviewed
西平賢作、山下篤、田中直子、川本理一朗、今村卓郎、山本隆一、北村和雄、浅田祐士郎
血圧 13 ( 9 ) 951 - 954 2006
Publishing type：Research paper (scientific journal)
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Effect of adrenomedullin administration on acetic acid-induced colitis in rats Reviewed
芦塚 伸也,石川 直人,加藤 丈司,山家 純一,稲津 東彦,北村 和雄,江藤 胤尚
Peptides 26 2610 - 2615 2005.12
Language：English Publishing type：Research paper (scientific journal)
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Long-term anti-hypertensive therapy with benidipine improves arterial stiffness over blood pressure lowering Reviewed
北 俊弘,Suzuki Y,江藤 胤尚,北村 和雄
Hypertens Res 28 959 - 964 2005.12
Language：English Publishing type：Research paper (scientific journal)