論文 - 北村 和雄
-
Adrenomedullin: A Possible Autocrine or Paracrine Inhibitor of Hypertrophy of Cardiomyocytes 査読あり
Tsuruda T., Kato J., Kitamura K., Kuwasako K., Imamura T., Koiwaya Y., Tsuji T., Kangawa K., Eto T.
Hypertension 31 ( 1 ) 505 - 510 1998年1月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Hypertension
Adrenomedullin (AM), a potent vasodilator peptide, exists in the cardiac ventricle; however, the role of AM in the ventricular tissue remains unknown. In the present study, we investigated the production and secretion of AM in cultured neonatal rat cardiomyocytes, and we examined the effect of AM on de novo protein synthesis in these cells by measuring [() C]phenylalanine incorporation. The cardiomyocytes cultured with serum-free media secreted AM into the media in a time-dependent manner at the rate of 12.2 +/- 0.5 fmol/10 cells/48 hours (mean +/- SEM). Angiotensin II (1 micro mol/L) or 10% fetal bovine serum significantly (P <.01) increased the AM secretion by 115% and 305%, respectively. In addition, Northern blot analysis of total RNA extracted from the myocytes disclosed the expression of prepro-AM mRNA of 1.6 kb. Synthetic AM at 1 micro mol/L significantly reduced the 10-6 mol/L angiotensin II- and 10% fetal bovine serum-stimulated [() C]phenylalanine incorporation into the cells, by 16% (P <.05) and 20% (P <.01), respectively. The inhibitory effect of AM on the angiotensin II-stimulated [() C]phenylalanine incorporation was abolished dose-dependently by a calcitonin gene-related peptide receptor antagonist, CGRP(8-37). Furthermore, blockade of the action of endogenous AM by either 10-6 mol/L CGRP(8-37) or anti-AM monoclonal antibody significantly enhanced the basal and 10-6 mol/L angiotensin II-stimulated [() C]phenylalanine incorporation. In summary, cultured neonatal rat cardiomyocytes produce and secrete AM, and the secreted AM inhibits the protein synthesis of these cells. Thus, AM may act on cardiomyocytes as an autocrine or a paracrine factor modulating the cardiac growth. (Hypertension. 1998;31[part 2]:505-510.). © 1998 Lippincott Williams & Wilkins, Inc.
-
Distribution and expression of adrenomedullin in human gastrointestinal tissue 査読あり
Kitani M., Sakata J., Asada Y., Kitamura K., Eto T.
Annals of Clinical Biochemistry 35 ( 5 ) 643 - 648 1998年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Annals of Clinical Biochemistry
Adrenomedullin (AM) is a biologically active peptide recently isolated from phaeochromocytoma. We report here the distribution and characterization of immunoreactive AM and gene expression of AM in human gastrointestinal tissue. Using a sensitive radioimmunoassay system for the peptide, immunoreactive human AM was detected in the stomach, duodenum, jejunum, ileum and colon. The AM concentration of these tissues was about 0.4-0.8 pmol/g wet tissue. Reverse phase and gel filtration high-performance liquid chromatographies showed that most of the immunoreactive AM in stomach and jejunum was identical to authentic human AM. By northern blot analysis, human AM mRNA was found to be expressed ubiquitously in the human gastrointestinal tissues. Furthermore, an immunohistochemical study revealed that immunoreactive AM cells were present in the gastrointestinal glands. These results suggest that AM may play some role as a gastrointestinal hormone.
-
Kita T., Kitamura K., Kuwasako K., Kawamoto M., Eto T.
Journal of Hypertension 16 ( 12 SUPPL. ) 2057 - 2062 1998年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Hypertension
Objective. Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are novel hypotensive peptides produced from the same precursor. A relationship between AM and the renin-angiotensin-aldosterone (RAA) axis was reported in several studies, but the response of the above two peptides to short-term modulation of the RAA axis in humans is not yet clear. Here, we assessed the responses of AM and PAMP in patients with varying RAA system status, including renovascular hypertension (RVH) and primary aldosteronism (PA). Design and methods. Essential hypertension (EHT), RVH and PA patients were hospitalized and maintained on a standard diet (NaCl 10 g/day). The patients underwent a captopril (25 mg) loading test. A renin-secretion stimulating test (furosemide 1 mg/kg, i.v. + 2 h of walking) and an ACTH loading test were performed for the PA patients. The plasma renin activity (PRA), plasma aldosterone concentration (PAC), and plasma AM and PAMP levels were monitored before and after the loadings. Results. In the basal state, significantly higher concentrations of AM and PAMP were shown in the RVH patients compared to the other groups. AM and PAMP were significantly correlated with PRA but not PAC in all patients. The AM and PAMP levels were not affected by the captopril loading with or without a hypotensive reaction. The AM and PAMP levels were increased only slightly despite the large increase in PAC induced in the PA patients by the renin-secretion stimulating and ACTH loading tests. Conclusion. The responses of plasma AM and PAMP to a short-term modulation of the RAA system were relatively small, despite the correlations observed between PRA and AM or PAMP.
-
アドレノメデュリンとPAMPの発見の経緯とその構造 査読あり
寒川賢治、北村和雄
医学のあゆみ 184 ( 1 ) 3 - 9 1998年
掲載種別：研究論文（学術雑誌）
-
アドレノメデュリンと関連ペプチド 査読あり
北村和雄
日本薬理学雑誌 112 ( 3 ) 137 - 146 1998年
掲載種別：研究論文（学術雑誌）
-
アドレノメデュリンとPAMP 査読あり
北村和雄
医学のあゆみ 185 ( 1 ) 71 - 74 1998年
掲載種別：研究論文（学術雑誌）
-
アドレノメデュリンおよび関連ペプチドの測定と問題点 査読あり
北村和雄
医学のあゆみ 184 ( 1 ) 21 - 25 1998年
掲載種別：研究論文（学術雑誌）
-
アドレノメデュリンおよび関連ペプチド 査読あり
北村和雄
循環科学 18 ( 12 ) 1132 - 1135 1998年
掲載種別：研究論文（学術雑誌）
-
循環器系疾患における血中成熟型および中間型アドレノメデュリンの動態と意義 査読あり
平山直輝、北村和雄、江藤胤尚
日本内分泌学会雑誌 74 ( 2 ) 621 - 621 1998年
掲載種別：研究論文（学術雑誌）
-
心血管系への生理作用 査読あり
石山雄一郎、北村和雄
医学のあゆみ 184 ( 1 ) 44 - 48 1998年
掲載種別：研究論文（学術雑誌）
-
アドレノメデュリンの心血管系及び交感神経系に対する作用への延髄最後野の関与 査読あり
斉田光彦、加藤和男、國武孝人、花森隆充、北村和雄、江藤胤尚、河南洋
日本内分泌学会雑誌 74 ( 2 ) 619 - 619 1998年
掲載種別：研究論文（学術雑誌）
-
バルーン頚動脈内皮傷害後の内膜肥厚に及ぼすアドレノメデュリン持続静注の効果の検討 査読あり
松井英三郎、加藤丈司、北村和雄、江藤胤尚、浅田祐士郎、住吉昭信
日本内分泌学会雑誌 74 ( 2 ) 619 - 619 1998年
掲載種別：研究論文（学術雑誌）
-
アドレノメデュリンによる循環調節 査読あり
江藤胤尚、北村和雄、加藤丈司
臨床高血圧 4 ( 3 ) 155 - 168 1998年
掲載種別：研究論文（学術雑誌）
-
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）
-
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.
-
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.
-
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.
-
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.
-
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.
-
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.