Papers - KITAMURA Kazuo
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Serino R., Ueta Y., Hara Y., Nomura M., Yamamoto Y., Shibuya I., Hattori Y., Kitamura K., Kangawa K., Russell J.A., Yamashita H.
Endocrinology 140 ( 5 ) 2334 - 2342 1999
Publishing type：Research paper (scientific journal) Publisher：Endocrinology
The effects of intracerebroventricular (icv) administration of adrenomedullin (AM) on plasma oxytocin (OXT), c-Fos protein (Fos), and c-fos messenger RNA (mRNA) in the paraventricular (PVN) and supraoptic nuclei (SON) of the rat were investigated using RIA for OXT, immunohistochemistry for Fos, and in situ hybridization histochemistry for c-Fos mRNA. Central administration of AM caused a significant increase in the plasma OXT level. Intracerebroventricular administration of AM caused a marked induction of Fos-like immunoreactivity (LI) in the PVN and in the dorsal parts of the SON. In the PVN and SON, OXT-LI cells predominantly exhibited nuclear Fos-LI in comparison with arginine vasopressin-LI cells. In situ hybridization histochemistry revealed that the induction of c-fos mRNA in the PVN and SON was increased in a dose-related manner 30 min after icv administration of AM. This induction was reduced by pretreatment with the AM receptor antagonist, human AM-(22-52)-NH2. These results suggest that central AM is responsible for activating the neurosecretory cells in the PVN and SON via selective AM receptors, and that AM stimulates the secretion of OXT by activating hypothalamic OXT-producing cells.
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アドレノメデュリンとその役割 Reviewed
北村和雄
CARDIAC PRACTICE 10 ( 3 ) 307 - 310 1999
Publishing type：Research paper (scientific journal)
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心肥大および心筋リモデリングにおけるオートクリン・パラクリン囲子としてのアドレノメデュリンの役割 Reviewed
鶴田敏博、加藤丈司、北村和雄、今村卓郎、小岩屋靖、江藤胤尚
血圧 6 ( 7 ) 661 - 664 1999
Publishing type：Research paper (scientific journal)
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プロアドレノメデュリン由来ペプチドの心血管系及び交感神経系作用に対する延髄最後野の関与 Reviewed
斉田光彦、國武孝人、北村和雄、江藤胤尚、河南洋
日本内分泌学会雑誌 75 ( 2 ) 441 - 441 1999
Publishing type：Research paper (scientific journal)
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アドレノメデュリンの中枢投与による腎交感神経活動の早期抑制反応と脳内オキシトシン受容体の関係 Reviewed
斉田光彦、加藤和男、國武孝人、北村和雄、江藤胤尚、河南洋
日本内分泌学会雑誌 75 ( 2 ) 332 - 332 1999
Publishing type：Research paper (scientific journal)
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癌性腹膜炎患者の血中ならびに腹水中におけるアドレノメデュリンの動態 Reviewed
清水昭彦、北村和雄、江藤胤尚
日本内分泌学会雑誌 75 ( 2 ) 442 - 442 1999
Publishing type：Research paper (scientific journal)
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新しい脈管作動物質アドレノメデュリンの役割 Reviewed
江藤胤尚、北村和雄、加藤丈司
最新医学 54 ( 5 ) 1015 - 1021 1999
Publishing type：Research paper (scientific journal)
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アドレノメデュリンの作用と細胞内情報伝達 Reviewed
桑迫健二、北村和雄
医学のあゆみ 191 ( 5 ) 405 - 411 1999
Publishing type：Research paper (scientific journal)
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Etoh T., Kato J., Takenaga M., Imamura T., Kitamura K., Koiwaya Y., Eto T.
Clinical Cardiology 22 ( 2 ) 113 - 117 1999
Publishing type：Research paper (scientific journal) Publisher：Clinical Cardiology
Background: Adrenomedullin (AM) is a potent vasodilatory peptide discovered in human pheochromocytoma tissue. Proadrenomedullin N-terminal 20 peptide (PAMP) processed from an AM precursor is also a novel hypotensive peptide which inhibits catecholamine secretion from sympathetic nerve endings. Hypothesis: The present study sought to examine the relationships between the two peptides and other clinical parameters by measuring the plasma AM and PAMP concentrations in 98 patients with heart failure. Methods: In all, 98 patients [65 men and 33 women, aged 58.2 ± 11.0 years, mean ± standard deviation (SD)] with heart failure and 26 healthy volunteers (12 men and 14 women, aged 54.1 ± 8.6 years) were examined in this study. Heart failure was secondary to previous myocardial infarction in 58 patients, valvular disease in 28, cardiomyopathy in 9, and congenital heart disease in 3. All patients were classified into two groups of class I or II (Group 1) and class III or IV (Group 2) according to the New York Heart Association (NYHA) functional classification. Results: Both plasma AM and PAMP concentrations in the patients were significantly higher than those in healthy volunteers. In addition, plasma AM and PAMP concentrations in patients in class III or IV of New York Heart Association (NYHA) classification were significantly higher than those in NYHA class I or II. The elevated plasma concentrations of these peptides in patients in NYHA class III or IV significantly decreased in response to the treatment for 7 days. There was a significant correlation between plasma AM and PAMP, though the plasma concentration of PAMP was one-fifth to one-seventh of that of AM in patients and controls. The plasma AM concentration correlated significantly with the plasma concentrations of atrial and brain natriuretic peptides, epinephrine, and right atrial pressure, whereas such a relationship was not noted for the plasma PAMP concentration. Conclusions: Judging from the difference in not only the biological actions but also the hormonal profiles between AM and PAMP, they may differentially modulate the cardiovascular system in patients with heart failure, although they are processed from the same precursor.
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Kinoshita H., Fujimoto S., Kitamura K., Yokota N., Kawamoto M., Tokura T., Hisanaga S., Eto T.
American Journal of Kidney Diseases 34 ( 1 ) 114 - 119 1999
Publishing type：Research paper (scientific journal) Publisher：American Journal of Kidney Diseases
· Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide present in the precursor of adrenomedullin (AM), a vasodilative and natriuretic peptide. We examined the plasma and urinary levels of these peptides in patients with chronic glomerulonephritis (CGN). The mean plasma AM concentration of the patients with CGN did not differ from that of control subjects (4.17 ± 0.17 v 3.87 ± 0.21 fmol/mL, respectively), whereas urinary AM excretion was significantly less in the patients with CGN (5.96 ± 0.95 v control, 8.93 ± 1.02 fmol/mg of creatinine; P < 0.05). Plasma concentrations and urinary excretion of PAMP were significantly less for the patients with CGN compared with control subjects (0.91 ± 0.08 v 1.23 ± 0.20 fmol/mL; P < 0.05 and 25.0 ± 3.0 v 35.0 ± 3.6 fmol/mg of creatinine, respectively; P < 0.05). The plasma AM concentration was negatively correlated with plasma renin activity (r = -0.58; P < 0.01) and aldosterone concentration (r = - 0.40; P < 0.05). Urinary excretions of AM and PAMP showed significant correlations with urine excretion of sodium (r 0.39; P < 0.05 and r = 0.49; P < 0.01, respectively). These findings suggest that AM and PAMP may have roles in the regulation of sodium in patients with CGN.
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Increased plasma proadrenomedullin N-terminal 20 peptide in patients with essential hypertension Reviewed
Kuwasako K., Kitamura K., Kangawa K., Ishiyama Y., Kato J., Eto T.
Annals of Clinical Biochemistry 36 ( 5 ) 622 - 628 1999
Publishing type：Research paper (scientific journal) Publisher：Annals of Clinical Biochemistry
The novel hypotensive peptide, proadrenomedullin N-terminal 20 peptide (PAMP), is processed from the adrenomedullin precursor. Recently, we identified PAMP-12 [PAMP(9-20)] from the porcine adrenal medulla as a major endogenous and biologically active peptide. Using a new, sensitive radioimmunoassay which recognizes the C-terminal region of PAMP-20 [PAMP(1-20)], we investigated the role of PAMP in patients with essential hypertension who had normal renal function, and whether PAMP-12 is present in humans. The mean PAMP plasma concentration, like that of adrenomedullin. was significantly higher in hypertensive [1.51 fmol/mL, standard error of the mean (SEM) 0.09 fmol/mL] than normotensive participants (1.08 fmol/mL, SEM 0.05). The increase in plasma PAMP concentration in patients with organ damage accompanied by hypertension was significantly higher than that in patients without organ damage. The PAMP concentration had a significant positive correlation with mean blood pressure and adrenomedullin concentration. The immunoreactive PAMP in human tissue and plasma was characterized by reverse-phase high-performance liquid chromatography, PAMP-12, as well as PAMP-20, was abundant in the phaeochromocytoma tissue. These findings suggest that PAMP plays some pathophysiological role against the development of essential hypertension.
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Autotransplantation and Stent Implantation for Bilateral Renal Artery Fibromuscular Dysplasia. Reviewed
Kyoraku Yuka, Kato Johji, Nishi Yuichi, Kita Toshihiro, Kitamura Kazuo, Asato Mikio, Tamura Shozo, Tanabe Kazunari, Toma Hiroshi, Eto Tanenao
Hypertension Research 22 ( 2 ) 141 - 143 1999
Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Hypertension
A 36-yr-old male was found to have renovascular hypertension due to an occluded right renal artery and 70% stenosis in the left renal artery, caused by fibromuscular dysplasia. The right kidney was supplied by collateral blood flow, and secreted more renin than the left kidney. Two differential therapeutic approaches were taken: autotransplantation for the right kidney and percutaneous transluminal renal angioplasty followed by stent implantation for the left. The renovascular hypertension was treated with these therapies, preserving renal function in this patient. (<i>Hypertens Res</i> 1999; 22: 141-143)
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Sakata J., Asada Y., Shimokubo T., Kitani M., Inatsu H., Kitamura K., Kangawa K., Matsuo H., Sumiyoshi A., Eto T.
Journal of Gastroenterology 33 ( 6 ) 828 - 834 1998.12
Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology
The aim of this study was to investigate the regional distribution, molecular forms, and gene expression of adrenomedullin in the rat gastrointestinal tract and to examine physiological changes in gastric adrenomedullin after 24-h fasting. The tissue concentration was measured by radioimmunoassay. The molecular forms were analyzed by high performance liquid chromatography. mRNA levels were quantified by Northern blotting and cells positive for adrenomedullin immunoreactivity were localized by immunohistochemistry. A high concentration of adrenomedullin was found in stomach, cecum, and colon (450-520 fmol/g wet tissue). Adrenomedullin immunoreactivity was also detected in duodenum, jejunum, and ileum (200-250 fmol/g wet tissue). Transcripts of the adrenomedullin gene were widely expressed throughout the gastrointestinal tract. The major form of adrenomedullin immunoreactivity in stomach and colon corresponded precisely with authentic adrenomedullin peptide. Adrenomedullin immunoreactive cells were present in the gastrointestinal endocrine system. The concentration and mRNA level of gastric adrenomedullin after fasting were significantly increased compared with findings in controls. Adrenomedullin is ubiquitous in the gastrointestinal tract, and may be produced by endocrine cells. The results suggest that adrenomedullin, through its potent vasodilating activity, may play some role, in the stomach including the regulation of the mucosal blood flow.
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Nagata N., Kato J., Kitamura K., Kawamoto M., Tanaka N., Eto T., Takasaki M.
European Journal of Endocrinology 139 ( 6 ) 611 - 614 1998.12
Publishing type：Research paper (scientific journal) Publisher：European Journal of Endocrinology
Adrenomedullin (AM), a potent vasodilator peptide, has been shown to act within the central nervous system to modulate fluid and electrolyte balance. AM-immunoreactive cells have been found in the anterior pituitary gland and the choroid plexus of humans. In addition, AM activity has been implicated in the regulation of maternal circulation during pregnancy. To determine the relationship between AM concentration in the cerebrospinal fluid (CSF) and plasma, we measured AM levels in CSF and plasma of pregnant (group P, n = 12) and non-pregnant (group NP, n = 10) women scheduled to undergo gynecologic or obstetric surgery. In both groups, the concentration of AM in the plasma exceeded that in the CSF. Plasma AM concentration was significantly higher in pregnant than nonpregnant women (17.3 ± 5.8 vs 5.1 ± 1.4 pmol/l, mean ± S.D.; P < 0.01), whereas CSP AM concentration did not differ between the two groups (1.3 ± 0.9 and 0.9 ± 0.4 pmol/l in groups P and NP respectively). No significant correlation was found between AM concentrations in the CSF and plasma. The present findings suggest that AM is present in the CSF and that its concentration in the CSF is regulated independently from that in the plasma.
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Adrenomedullin regulation by thyroid hormone in the rat Reviewed
Murakami Y., Hattori Y., Taniyama M., Kitamura K., Kasai K.
Life Sciences 63 ( 24 ) PL337 - PL342 1998.11
Publishing type：Research paper (scientific journal) Publisher：Life Sciences
To investigate the effect of thyroid hormone on adrenomedullin (AM) changes during hyper- and hypothyroid states, we evaluated plasma AM concentrations and AM mRNA levels in lung tissue from hyper- and hypothyroid rats. AM peptide concentrations were significantly higher in plasma from hyperthyroid rats and lower in plasma from hypothyroid rats compared with control rats. AM mRNA transcripts were significantly increased in lung tissue from hyperthyroid rats and significantly decreased in lung tissue from hypothyroid rats compared with normal rats. These changes are paralleled alterations in AM production in cultured rat vascular smooth muscle cells, in which AM is regulated at the transcriptional level by thyroid hormone. Thus, thyroid hormone positively regulates AM production in vivo.
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Saita M., Ishizuka Y., Kato K., Kunitake T., Hanamori T., Kitamura K., Eto T., Kannan H.
Regulatory Peptides 77 ( 1-3 ) 147 - 153 1998.10
Publishing type：Research paper (scientific journal) Publisher：Regulatory Peptides
Proadrenomedullin NH2-terminal 20 peptide (PAMP) and adrenomedullin (AM), which are derived from the same gene, are novel vasodilative peptides and have been shown to exhibit hypotensive action in anesthetized animals. To avoid the modification via anesthesia, we investigated the effects of intravenously administered PAMP on mean arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) relative to those of AM in conscious unrestrained rats. We also examined whether the arterial baroreceptor reflex was altered with the two peptides. Intravenous injection of rat PAMP (rPAMP) (10, 20 and 50 nmol/kg) and rat AM (rAM) (0.3, 1.0 and 3.0 nmol/kg) similarly elicited dose-related hypotension accompanied by increases in HR and RSNA. However, the responses to rPAMP were less potent in magnitude and shorter in duration than those to rAM. Moreover, rAM facilitated baroreflex control, whereas rPAMP attenuated it. These findings indicate that although PAMP, as well as AM, may play an important role as a circulating hormone in the systemic circulation of conscious rats, the two peptides derived from an identical origin might have different mechanisms responsible for their cardiovascular and RSNA actions. Copyright (C) 1998 Elsevier Science B.V.
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Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage Reviewed
Kikumoto K., Kubo A., Hayashi Y., Minamino N., Inoue S., Dohi K., Kitamura K., Kangawa K., Matsuo H., Furuya H.
Anesthesia and Analgesia 87 ( 4 ) 859 - 863 1998.10
Publishing type：Research paper (scientific journal) Publisher：Anesthesia and Analgesia
Adrenomedullin (AM) is a potent hypotensive peptide originally identified in pheochromocytoma tissues. Impaired cardiovascular conditions, such as hypertension, myocardial infarction, and septic shock, stimulate production of AM. This study was performed to determine whether subarachnoid hemorrhage (SAH) altered plasma AM concentration. Plasma concentrations of AM in 17 patients with SAH were measured for 2 wk after the onset of SAH by AM- specific radioimmunoassay. Plasma concentrations of AM were increased in patients with SAH throughout the study period, compared with those in control subjects. Plasma concentrations of AM in patients classified as Hunt and Kosnik grade III or IV were significantly higher than those classified as Hunt and Kosnik grade I or II on the day of and the day after the onset of SAH. However, plasma concentrations of AM were unaffected by angiographic vasospasm. These findings suggest that plasma concentrations of AM are increased in patients with SAH and may reflect the severity of SAH. Implications: Adrenomedullin has been reported to affect the cerebral circulation. This study was performed to determine whether subarachnoid hemorrhage, a typical cerebrovascular disorder, altered plasma adrenomedullin concentrations. We found that plasma adrenomedullin concentrations increased in patients with Subarachnoid hemorrhage, although no relationship was found between plasma adrenomedullin concentration and angiographic vasospasm. Plasma adrenomedullin concentration may reflect the severity of hemorrhage.
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Adrenomedullin and related peptides. Reviewed
KITAMURA Kazuo
Folia Pharmacologica Japonica 112 ( 3 ) 137 - 146 1998.9
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Pharmacological Society
“Adrenomedullin (AM)” is a novel hypotensive peptide discovered in human pheochromocytoma by monitoring the elevating activity of platelet cAMP. It has potent and long-lasting vasodilator effects in several vascular systems. In addition, a novel 20-residue hypotensive peptide, termed “proadrenomedullin N-terminal 20 peptide” (PAMP), is processed from proadrenomedullin. Although initially isolated from human pheochromocytoma tissue and porcine adrenal medullae, AM mRNA is highly expressed in several organs including cardiovascular tissues. Taken together with its widespread distribution and its ability to influence the bioactivity of cells <I>in situ</I>, AM may function as a paracrine or autocrine hormone rather than a classical endocrine system. Furthermore, ubiquitous expression of AM mRNA may indicate its various biological functions as well as the existence of a novel circulation control system. Plasma AM as well as PAMP concentrations significantly increased in various cardiovascular diseases including hypertension, chronic renal failure and congestive heart failure. The present review summarizes the recent advances in AM research and showed that AM and PAMP are important vasoactive peptides, such investigations should enable the elucidation of the basic physiologic mechanisms of novel circulatory homeostasis.
DOI： 10.1254/fpj.112.137
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Measurement of plasma and urinary adrenomedullin in patients with IgA nephropathy Reviewed
Kubo A., Iwano M., Minamino N., Sato H., Nishino T., Hirata E., Akai Y., Shiiki H., Kitamura K., Kangawa K., Matsuo H., Dohi K.
Nephron 78 ( 4 ) 389 - 394 1998.4
Publishing type：Research paper (scientific journal) Publisher：Nephron
In this study, we measured plasma and urinary adrenomedullin (AM) concentrations in 47 patients with IgA nephropathy. Controls were 39 healthy volunteers. Plasma and urinary AM values were measured by specific radioimmunoassay. The plasma AM concentrations were higher, and the urinary AM levels were lower in patients with IgA nephropathy than in healthy volunteers. Plasma AM concentrations showed a positive correlation with serum creatinine and blood urea nitrogen, whereas urinary AM levels correlated negatively with serum creatinine and blood urea nitrogen. The plasma AM concentrations showed a positive correlation with fractional excretions of sodium and potassium. Renal biopsy specimens of patients without renal failure were scored for activity (percentage of glomeruli demonstrating cellular crescent formation, degree of mesangial proliferation and interstitial infiltration; total score = 9). Urinary AM levels were shown to be lower in the group with a high activity (score 3-9) as compared with the group with a low activity (score 0-2) based on renal biopsy. Thus, urinary levels of AM are affected by the degree of the activity in IgA nephropathy, and AM may participate in the pathophysiology of IgA nephropathy.
DOI： 10.1159/000044966
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Saita M., Shimokawa A., Kunitake T., Kato K., Hanamori T., Kitamura K., Eto T., Kannan H.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology 274 ( 4 43-4 ) R979 - R984 1998.4
Publishing type：Research paper (scientific journal) Publisher：American Journal of Physiology - Regulatory Integrative and Comparative Physiology
Adrenomedullin (ADM) is reported to be a peripherally acting hypotensive peptide, but its central actions are unclear. We investigated the effects of centrally administered ADM on blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. We also investigated the receptors interacting with ADM using two putative antagonists. Intracerebroventricular administration of ADM in doses of 0.1 and 0.5 nmol/kg caused tachycardia and early inhibition of RSNA. Central ADM (1.0 nmol/kg) induced hypertension, tachycardia, and a decrease followed by an increase in RSNA. In SAD rats, increases in BP, HR, and RSNA at the late phase were enhanced by central ADM (1.0 nmol/kg), whereas the early decrease in RSNA remained. Thus the inhibition of RSNA via central ADM may be unrelated to the arterial baroreceptor reflex. Pretreatment with antagonists human calcitonin gene-related peptide-(8-37) and human ADM-(22- 52) significantly suppressed the central actions of ADM. The findings suggest that ADM is involved as a neuropeptide in the receptor-mediated central regulation of the cardiovascular system and RSNA.