The regulation mechanism of brain angiotensin II

• Project/Area Number: 18590945
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kagawa University
• Principal Investigator: HOSOMI Naohisa Kagawa University, 医学部, 助教 (70363190)
• Co-Investigator(Kenkyū-buntansha): NAYA Takayuki 香川大学, 医学部, 助教 (80398031) ; KOUNO Masakazu 香川大学, 医学部, 教授 (20153489) ; NISHIYAMA Akira 香川大学, 医学部, 教授 (10325334) ; KIMURA Syouji 香川大学, 医学部, 教授 (30253264)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,070,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥570,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: 脳・神経 / 血液脳関門 / アンジオテンシンII / 細胞間基質 / インテグリン / 脳 / アンジオテンシン受容体拮抗薬 / アンギオテンシンII

Research Abstract

ARBあるいはAT2受容体拮抗薬の全身投与が脳組織アンジオテンシンII濃度を低下させ、血中アンジオテンシンIIの脳組織への移行はかなり限定されていることが示唆された。またARBの全身投与による脳組織アンジオテンシンII濃度の低下に脳組織AGT、ACE mRNAの抑制が関与している可能性が示唆された。また、AT2受容体拮抗薬(PD123319)投与によっても脳組織アンジオテンシンII濃度の低下を軽度認めたが、これは、脳組織AGT mRNAの抑制が関与していることが示唆された。

Research Products

• [Journal Article] The expression of matrix metalloproteinase-13 (MMP3) is ineased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model (2009)
  • Author(s): Ueno M, Wu B, Nishiyama A, Huang C, Hosomi N, Kusaka T, Nakagawa T, Onodera M, Kido M, Sakamoto H
  • Journal Title: Hypertens Res
  • Peer Reviewed
• [Journal Article] Tissue Doppler echocardiography for predicting arterial stiffnes aessed by cardio-anke vascular ndex (2009)
  • Author(s): Masugata H, Senda S, Goda F, YamA, Okuyama H, Kohno T, Hosomi N, Yukiiri K, Noma T, Kiyomoto H, Murao K, Nishiyama A, Kohno M
  • Journal Title: Tohoku J Exp Med 217 Pages: 139-146
  • Peer Reviewed
• [Journal Article] Neurovascular UniのアンチエージングとRAS (2009)
  • Author(s): 細見直永、河野雅和
  • Journal Title: Angiotensin Research 6 Pages: 104-110
  • Peer Reviewed
• [Journal Article] The expression of matrix metalloproteinase-13 (MMP-13) is increased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model. (2009)
  • Author(s): Ueno M
  • Journal Title: Hypertens Res. (未定)(印刷中)
  • Peer Reviewed
• [Journal Article] Tissue Doppler echocardiography for predicting arterial stiffness assessed by cardio-ankle vascular index. (2009)
  • Author(s): Masugata H
  • Journal Title: Tohoku J Exp Med. 217 Pages: 139-146
  • Peer Reviewed
• [Journal Article] Neurovascular UnitのアンチェージングとRAS. (2009)
  • Author(s): 細見 直永
  • Journal Title: Angiotensin Research 6 Pages: 104-110
• [Journal Article] Differences in left ventricular hypertrophy and dysfunction betwee patients ith cerebral hemorrhage and those with cerebral infarction (2008)
  • Author(s): Masugata H, Senda S, Goda F, YamagaA, Okuyama H, Kohno T, Hosomi N, Imai M, Yukiiri K, Kohno M
  • Journal Title: Tohoku J Exp Med 215 Pages: 159-165
  • Peer Reviewed
• [Journal Article] Possible involvement of Rho-kinase in aldosterone-iducevascular smth muscle cell remodeling (2008)
  • Author(s): Miyata K, Hitomi H, Guo P, Zhang GX, Kimura S, Kiyomoto H, Hosomi N, Kagami S, Kohno M, Nishiyama A
  • Journal Title: Hypertens Res 31 Pages: 1407-1413
  • Peer Reviewed
• [Journal Article] Strict angiotensin blockade prevents the augmentation of intrarenal angioensin II and podocyte abnormalitiesn ty 2 diatic rats with microalbuminuria (2008)
  • Author(s): Nishiyama A, Nakagawa T, Koori Nagai Y, Okada N, Konishi Y, Morikawa T, Okumura M, Meda I, Kiyomoto H, Hosomi N, Mori T, Ito S, Imanishi M
  • Journal Title: J Hypertens 26 Pages: 1849-1859
  • Peer Reviewed
• [Journal Article] Differences in left ventricular hypertrophy and dysfunction between patients with cerebral hemorrhage and those with cerebral infarction. (2008)
  • Author(s): Masugata H
  • Journal Title: Tohoku J Exp Med. 215 Pages: 159-165
  • Peer Reviewed
• [Journal Article] Possible involvement of Rho-kinase in aldosterone-induced vascular smooth muscle cell remodel ing. (2008)
  • Author(s): Miyata K
  • Journal Title: Hypertens Res. 31 Pages: 1407-1413
  • Peer Reviewed
• [Journal Article] Strict angiotensin blockade prevents the augmentation of intrarenal angiotens in II and podocyte abnormalities in type 2 diabetic rats with microalbuminuria. (2008)
  • Author(s): Nishiyama A
  • Journal Title: J Hypertens. 26 Pages: 1849-1859
  • Peer Reviewed
• [Journal Article] Left ventricular diastolic dysfunction in normotensive diabetic patients in variousage strata (2008)
  • Author(s): Masugata H, et. al.
  • Journal Title: Diabetes Res Clin Pract. 79 Pages: 91-96
  • Peer Reviewed
• [Journal Article] RASと虚血障害 (2007)
  • Author(s): 細見直永、河野雅和
  • Journal Title: Angiotensin Research 4 Pages: 241-248
• [Journal Article] Smoking,fasting serum insulin,and obesity are the predictor of carotid atherosclerosis in relatively young subjects (2007)
  • Author(s): Naya T, et. al.
  • Journal Title: Angiology. 58 Pages: 677-684
  • Peer Reviewed
• [Journal Article] Relation of Postischemic Delayed Hypoperfusion and Cerebral Edema after Transient Forebrain Ischemia (2007)
  • Author(s): Hosomi N, et. al.
  • Journal Title: J Stroke Cerebrovasc Dis. 16 Pages: 103-108
  • Peer Reviewed
• [Journal Article] The Japan Standard Stroke Registry Study Group: Efficacy of anti-coagulant treatment with argatroban on cardioembolic stroke (2007)
  • Author(s): Hosomi N, et. al.
  • Journal Title: J Neurol. 254 Pages: 605-612
  • Peer Reviewed
• [Journal Article] Latent cardiac dysfunction as assessed by echocardiography in bed-bound patients following cerebrovascular accidents: comparison with nutritional status (2007)
  • Author(s): Masugata H, et. al.
  • Journal Title: Int Heart 48 Pages: 505-512
  • Peer Reviewed
• [Journal Article] Cardiac function as assessed by echocardiography in the oldest old>or=90years of age (2007)
  • Author(s): Masugata H, et. al.
  • Journal Title: Int Heart 48 Pages: 497-504
  • Peer Reviewed
• [Journal Article] Granulocyte colony-stimulating factor facilitates the angiogenesis induced by ultrasonic microbubble destruction (2007)
  • Author(s): Miyake Y, et. al.
  • Journal Title: Ultrasound Med Biol. 33 Pages: 1796-1804
  • Peer Reviewed
• [Journal Article] Aldosterone suppresses insulin signaling via the downregulation of insulin receptor substrate-1 in vascular smooth muscle cells (2007)
  • Author(s): Hitomi H, et. al.
  • Journal Title: Hypertension 50 Pages: 750-755
  • Peer Reviewed
• [Journal Article] Role of mitochondria in angiotensin II-induced reactive oxygen species and mitogen-activated protein kinase activation (2007)
  • Author(s): Zhang GX, et. al.
  • Journal Title: Cardiovasc Res. 76 Pages: 204-212
  • Peer Reviewed
• [Journal Article] Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases (2007)
  • Author(s): Zhang GX, et. al.
  • Journal Title: Am J Physiol Heart Circ Physiol. 50
  • Peer Reviewed
• [Journal Article] Angiotensin II and oxidative stress (2007)
  • Author(s): Hitomi H, et. al.
  • Journal Title: Curr Opin Cardiol. 22 Pages: 311-315
  • Peer Reviewed
• [Journal Article] Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice (2007)
  • Author(s): Zhang GX, et. al.
  • Journal Title: J Mol Cell Cardiol. 42 Pages: 804-811
  • Peer Reviewed
• [Journal Article] Effects of adrenomedullin 2 on regional hemodynamics in conscious rats. (2007)
  • Author(s): Fujisawa Y, et. al.
  • Journal Title: Eur J Pharmacol. 558 Pages: 128-132
  • Peer Reviewed
• [Journal Article] Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes. (2007)
  • Author(s): Chen Y
  • Journal Title: Circ J. 71・1 Pages: 144-152
• [Journal Article] Effects of adrenomedullin on cardiac oxidative stress and collagen accumulatio in aldoseroneependent malignant hypertensive rats (2006)
  • Author(s): Rahman M, Nishiyama A, Guo P, Nagai Y, Zhang GX, Fujisawa Y, Fan YY, Kimura S, Hosomi N, Omori K, Abe Y, Kohno M
  • Journal Title: J Pharmacol Exp Ther 318 Pages: 1323-1329
  • Peer Reviewed
• [Journal Article] Augmentationof intrareal angiotensin els in uninephrectomd osterone/slt -treated hypertensive rats ; renoprotece effects of an ahigh dose of olmesartan (2006)
  • Author(s): Fan YY, Baba R, Nagai Y, Miyatake Hosomi N, Kimura S, Sun GP, Kohno M, Fujita M, Abe Y, Nishiyama A.
  • Journal Title: Hypertens Res 29 Pages: 169-178
  • Peer Reviewed
• [Journal Article] Relation of Postischemic Delayed Hypoperfusion and Cerebral Edema following Transient Forebrain Ischemia. (2006)
  • Author(s): Hosomi N
  • Journal Title: J Stroke Cerebrovasc Dis. (in press)
• [Journal Article] Efficacy of anti-coagulant treatment with argatroban on cardioembolic stroke. (2006)
  • Author(s): Hosomi N
  • Journal Title: J Neurol. (in press)
• [Journal Article] Smoking, fasting serum insulin, and obesity are the predictor of carotid atherosclerosis in relatively young subjects. (2006)
  • Author(s): Naya T
  • Journal Title: Angiology (in press)
• [Journal Article] Interferon-gamma enhances superoxide production in human mesangial cells via the JAK-STAT pathway. (2006)
  • Author(s): Moriwaki K
  • Journal Title: Kidney Int. 70・4 Pages: 788-793
• [Journal Article] Involvements of Rho-kinase and TGF-beta pathways in aldosterone-induced renal injury. (2006)
  • Author(s): Sun GP
  • Journal Title: J Am Soc Nephrol. 17・8 Pages: 2193-2201
• [Journal Article] Effects of adrenomedullin on cardiac oxidative stress and collagen accumulation in aldosterone-dependent malignant hypertensive rats. (2006)
  • Author(s): Rahman M
  • Journal Title: J Pharmacol Exp Ther. 318・3 Pages: 1323-1329
• [Journal Article] Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats : renoprotective effects of an ultrahigh dose of olmesartan. (2006)
  • Author(s): Fan YY
  • Journal Title: Hypertens Res. 29・3 Pages: 169-178
• [Journal Article] Contribution of reactive oxygen species to the pathogenesis of left ventricular failure in Dahl salt-sensitive hypertensive rats : effects of angiotensin II blockade. (2006)
  • Author(s): Guo P
  • Journal Title: J Hypertens. 24・6 Pages: 1097-1104
• [Journal Article] Synergistic effect of mechanical stretch and angiotensin II on superoxide production via NADPH oxidase in vascular smooth muscle cells. (2006)
  • Author(s): Hitomi H
  • Journal Title: J Hypertens. 24・6 Pages: 1089-1095
• [Journal Article] Effects of adrenomedullin 2 on regional hemodynamics in conscious rats. (2006)
  • Author(s): Fujisawa Y
  • Journal Title: Eur J Pharmacol. (in press)
• [Presentation] Role of ARB on blood-brain barrier permeability and cognitive disorders in Dahl salt sensitive rats (2009)
  • Author(s): Pelisch N, 細見直永, 上野正樹, 西山成, 河野雅和
  • Organizer: 第34回日本脳卒中学会
  • Place of Presentation: 松江
  • Year and Date: 2009-03-22
• [Presentation] The regulation of brain renin-angiotensin system with systemic ARB treatment (2009)
  • Author(s): Pelisch N, 細見直永山成, 河野雅和
  • Organizer: 第34回日本脳卒中学会
  • Place of Presentation: 松江
  • Year and Date: 2009-03-22
• [Presentation] The regulation of brain renin-angiotensin system with systemic ARB treatment. (2009)
  • Author(s): Pelisch N
  • Organizer: 第34回日本脳卒中学会
  • Place of Presentation: 松江
  • Year and Date: 2009-03-22
• [Presentation] Role of ARB on blood-brain barrier permeability and cognitive di sorders in Dahl salt sensitive rats. (2009)
  • Author(s): Pelisch N
  • Organizer: 第34回日本脳卒中学会
  • Place of Presentation: 松江
  • Year and Date: 2009-03-22
• [Presentation] Role of candesartan in the regulatio of brain renin-angiotensin system (2008)
  • Author(s): Pelisch N, 細見直永, 劉鋼, 大北弘幸, 納谷貴之, 向井麻央, 西山成, 河野雅和
  • Organizer: 第20回日本脳循環代謝学会総会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-06
• [Presentation] Role of candesartan in the regulation of brain renin-angiotensin system. (2008)
  • Author(s): Pelisch N
  • Organizer: 第20回日本脳循環代謝学会総会.
  • Place of Presentation: 東京
  • Year and Date: 2008-11-06
• [Presentation] Brain angiotensin II increasd following focal cerebral ischemia (2008)
  • Author(s): Fu H, Hosomi N, Pelisch N, Liu G, Naya T, Ohkita H, Kobayashi H, Nishiyama A, Kohno M
  • Organizer: International symposium for the establishment of sustainable and recycling-based society
  • Place of Presentation: 高松
  • Year and Date: 2008-10-17
• [Presentation] Brain angiotensin II regulaton with sysemic angiotenin type 1 receptor blocker. (2008)
  • Author(s): Pelisch N, Hosomi N, Liu G, Fu H, Naya T, Ohkita H, Mukai M, Nishiyama A, Kohno M.
  • Organizer: Internonasymposiumfor the establishment of sustainable and recycling-based society
  • Place of Presentation: 高松
  • Year and Date: 2008-10-17
• [Presentation] Brain angiotensin II regulation with systemic angiotens intype 1 receptor blocker. (2008)
  • Author(s): Pelisch N
  • Organizer: International symposium for theestablishment of sustainable andrecycling-based society
  • Place of Presentation: 高松
  • Year and Date: 2008-10-17
• [Presentation] Brain angiotensin II increased following focal cerebral ischemia. (2008)
  • Author(s): Fu H
  • Organizer: International symposium for theestablishment of sustainable and recycling-based society
  • Place of Presentation: 高松
  • Year and Date: 2008-10-17
• [Presentation] 局所脳虚血後における脳組織アンギオンテンシIIの変化 (2008)
  • Author(s): 付華, 細見直永, Pelisch Nicolas, 劉鋼, 納谷貴之, 大北弘幸, 向井麻央, 西山成, 河野雅和
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-10
• [Presentation] Role of candesartan in the regulationof bain renin-angotensin system (2008)
  • Author(s): Pelisch N, Hosomi N, kobayashi S, Fu H Liu G, Ohkita H, Naya T, Mukai M, Ueno M, Miyatake A, Nishiyama A, Kohno M
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-10
• [Presentation] Role of candesartan in the regulation of brain renin-angiotensinsystem. (2008)
  • Author(s): Pelisch N
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-10
• [Presentation] 局所脳虚血後における脳組織アンギオンテンシンIIの変化. (2008)
  • Author(s): 付華
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-10
• [Presentation] Brain angiotensin II expresson increase following foal cerebral ischemia (2008)
  • Author(s): Hosomi N, Fu H, Pelisch N, Liu G, Naya T, Ohkita H, Kobayashi S, Nishiyama A, Kohno M
  • Organizer: 6th World Stroke Congress
  • Place of Presentation: ウィ-ン(オーストリア)
  • Year and Date: 2008-09-25
• [Presentation] Role of candesartan in the regulation of brain renin-angiotensin system (2008)
  • Author(s): Pelisch N, Hosomi N, Kobayashi S, Fu H, Liu G, Ohkita H, Naya T, Miyake A, Ueno M, Nishiyama A, Kohno M
  • Organizer: 6th World Stroke Congress
  • Place of Presentation: ウィ-ン(オーストリア)
  • Year and Date: 2008-09-25
• [Presentation] Effects of angiotensin II stimulation of astrocytes (2008)
  • Author(s): Hosomi N, Kobayashi S, Pelisch N, FuH, Liu G, Ohkita H, Naya T, Nishiyama A, Kohno M
  • Organizer: 6th World Stroke Congress
  • Place of Presentation: ウィ-ン(オーストリア)
  • Year and Date: 2008-09-25
• [Presentation] Effects of angiotensin II stimulation of astrocytes. (2008)
  • Author(s): Hosomi N
  • Organizer: 6th World stroke Congress.
  • Place of Presentation: ウィーン(オーストリア)
  • Year and Date: 2008-09-25
• [Presentation] Role of candesartan in the regulation of brain renin-angiotensin system. (2008)
  • Author(s): Pelisch N
  • Organizer: 6th World Stroke Congress
  • Place of Presentation: ウィーン(オーストリア)
  • Year and Date: 2008-09-25
• [Presentation] Brain angiotensin II expression increased following focal cerebral ischemia. (2008)
  • Author(s): Hosomi N
  • Organizer: 6th World Stroke Congress
  • Place of Presentation: ウィーン(オーストリア)
  • Year and Date: 2008-09-25
• [Presentation] 虚血性脳血管障害患者における早朝高血圧治療のための降圧剤の至適内服時期 (2008)
  • Author(s): 細見 直永, 等
  • Organizer: 第33回日本脳卒中学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-03-20
• [Presentation] Efficacy of Anti-Coagulant Treatment with Argatroban on Cardioembolic Stroke-JSSRS (2007)
  • Author(s): Hosomi N, et. al.
  • Organizer: 2nd Asian Stroke Forum
  • Place of Presentation: Kyoto
  • Year and Date: 2007-09-08
• [Presentation] 脳梗塞急性期血圧コントロール・脳内レニン・アンギオテンシン系阻害の有用性 (2007)
  • Author(s): 細見 直永, 等
  • Organizer: 第25回日本老年医学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2007-06-22
• [Remarks]
  • URL: http://www.kms.ac.jp/~ninai/stroke/index.html