1990 Fiscal Year Annual Research Report

高血圧性血管病変と生体内血管作動性ペプチドの関係

Research Project

Project/Area Number	01044120
Research Institution	Yokohama City University
Principal Investigator	塩之入洋横浜市立大学, 医学部, 講師 (20128599)
Co-Investigator(Kenkyū-buntansha)	BRUNNER Hans ローザンヌ大学, 医学部(スイス国), 教授 SAMBHI Mohun カリフォルニア大学, 医学部(米国), 教授 CHOBAMIAN Ar 米国、ボストン大学, 医学部, 教授高崎泉横浜市立大学, 医学部, 医員広瀬茂久東京工業大学, 理学部, 教授 (10134199)
Keywords	レニン / アルドステロン / プロスタグラジン / フィブロネクチン / アンジオテンシン変換酵素 / 高血圧 / 血管障害 / 動脈硬化
Research Abstract	ヒト血漿中の活性型レニンの直接測定方法を改良した。この測定方法による、ヒト静脈カテ-テル法によって部位別に採取した静臓血標本の測定を行った。その結果、血管作動性物質である酵素レニンは腎において産生分泌され、肝において代謝されることを明らかにした。遺伝子工学的手法を用いて、二次性高血圧症である原発性アルドステロン症患者の腎および副腎におけるレニン遺伝子の発現について検討した。その結果、原発性アルドステロン症では、腎・副腎組組におけるレニン遺伝子(mRNA)は完全に抑制されており、この遺伝子発現は降圧薬治寮に変動することも初めて明らかにした。臨床高血圧において、糖・脂質代謝の増悪は動脈硬化を促進をする。アンジオテンシン変換酵素阻害薬(シラザプリル、リシノプリル)は、高血圧長期治療に有効であり、糖・脂質代謝を良好に保つことを明らかにした。これは心血管系危険因子を改善する可能性をもつ。家兔大動脈血管内皮損傷は、血管作動性物質プロスタサイクリンの産生は障害し、血管障害進展に関することを明かにした。アンジオテンシン変換酵素阻害薬(リシノプリル、デラプリル)は血管作動性物質アンジオランシンII生成を抑制し、血圧を良好に下降させるが、腎機能障害をもつ高血圧患者では、これら薬物の体内殊存率が高いので、使用上の注意が必要であることを報告した。高血圧実験動物の高血圧と加齢による血管病変の検討を行った。その結果、血圧上昇と加齢はいずれも血管細胞外基質フィブロネクチン増加と血管平滑筋細胞の増加に密接に関与し、その増加にはフィブロネクチン遺伝子(mRNA)発現増強が関与することを初めて明らかにした。また降圧薬治療はこれら症変を改善することを明らかにした。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Hiroshi Shionoiri,Izumi Takasaki,et al.: "Measurement of plasma active renin by solid phase radioimmunoassay using monoclonal antibodies." American Journal of Medical Sciences. 300. 138-143 (1990)
[Publications] Izumi Takasaki,Aram V.Chobanian,et al.: "Effect of hypertension on fibronectine expression in the rat aorta." Journal of Biological Chemistry. 265. 21935-21939 (1990)
[Publications] Hiroshi Shionoiri,Shinichiro Ueda,et al.: "Glucose and lipid metabolism during longーterm lisinopril therapy in hypertensive patients." Journal of Cardiovascular Pharmacology. 16. 905-909 (1990)
[Publications] Izumi Takasaki,Aram V.Chobanian,et al.: "Effect of endotherial cell denudation on fatty acid metabolism by rabbit aorta." American Journal of Physiology. 259. H442-H447 (1990)
[Publications] Hiroshi Shionoiri,Kohsuke Minamisawa,et al.: "Pharmacokinetics and antihypertensive effects of lisinopril in hypertensive patients with noraml and impaired renal function." Journal of Cardiovascular Pharmacology. 16. 564-600 (1990)
[Publications] Takeshi Mizuno,Shigehisa Hirose,et al.: "Radioreceptor assay for atrial natriuretic peptide using purified recptor." Biomedical Research. 11. 29-34 (1990)
[Publications] Hiroshi Shinoiri,Kohichi Sugimoto,et al.: "Clucose and lipid metabolism during longーterm treatment with cilazapril in hypertensive patients with or without impaired glucose metabolism." Journal of Cardiovascular Pharmacology. 15. 933-938 (1990)
[Publications] Mohinder P.Sambhi,et al.: "Selectively enhanced stimulation of DNA synthesis by EGF in vascular smooth muscle cell from SHR." Clinical and Experimental Hypertension. 12 A. 307-316 (1990)
[Publications] Aram V.Chobanian,et al.: "Adaptive and maladaptive responses of the arterial wall to hypertension." Hypertension. 15. 666-674 (1990)
[Publications] Aram V.Chobanian,et al.: "The effect of ACE inthibitors and other antihypertensive drugs on cardiovascular risk factors and atherogenesis." Clinical Cardiology. 13 Suppl.43-48 (1990)
[Publications] Hans R.Brunner,et al.: "The reninーangiotensin system in hypertension." Hospital Practice. 25. 71-81 (1990)
[Publications] Hans R.Brunner,et al.: "Prevention of renal hypertension in the rat by neuropeptide Y." Journal of Hypertension. 8. 21-25 (1990)
[Publications] Hiromi Hagiwara,Shigehisa Hirose,et al: "Properties of rat uterus endothelin receptor site." Biomedical Research. 11. 93-98 (1990)
[Publications] Kohsuke Minamisawa,Hiroshi Shionoiri,et al.: "Depressor effects and pharmacokinetics of single and consecutive doses of delapril in hypertensive patients with normal or impaired renal function." Cardiovascular Drugs and Therapy. 4. 1417-1424 (1990)
[Publications] Masamichi Kozuka,Shigehisa Hirose,Hiromi Hagiwara,et al.: "Endothelin action on rat uterus is inhibited by an inhibitor of protein Kinase C and by inhibitors of the phospolipase A_2ーarachidonic acdーlipoxygenase pathway." Biomedical Research. 11. 287-289 (1990)
[Publications] Hiromi Hagiwara,Shigehisa Hirose,et al.: "Solubilization of endothelin receptors from bovine lung plasma membranes in a nonーaggregated state and estimation of their minimal function sizes." Biochemical and Biophysical Reserch Communications. 172. 576-581 (1990)
[Publications] Aram V.Chobanian,et al.: "Stressーinduced protein in aortic smooth muscle cells and aorta of hypertensive rats." American Journal of Physiology. 258. H1699-H1705 (1990)
[Publications] Hans R.Brunner,et al.: "Treating the individual hypertensive patients:Consideration on dose,sequential monotherapy and drug combination." Journal of Hypertension. 8. 3-11 (1990)

1990 Fiscal Year Annual Research Report

高血圧性血管病変と生体内血管作動性ペプチドの関係

Principal Investigator

塩之入 洋 横浜市立大学, 医学部, 講師 (20128599)

Research Products

[Publications] Hiroshi Shionoiri,Izumi Takasaki,et al.: "Measurement of plasma active renin by solid phase radioimmunoassay using monoclonal antibodies." American Journal of Medical Sciences. 300. 138-143 (1990)

[Publications] Izumi Takasaki,Aram V.Chobanian,et al.: "Effect of hypertension on fibronectine expression in the rat aorta." Journal of Biological Chemistry. 265. 21935-21939 (1990)

[Publications] Hiroshi Shionoiri,Shinichiro Ueda,et al.: "Glucose and lipid metabolism during longーterm lisinopril therapy in hypertensive patients." Journal of Cardiovascular Pharmacology. 16. 905-909 (1990)

[Publications] Izumi Takasaki,Aram V.Chobanian,et al.: "Effect of endotherial cell denudation on fatty acid metabolism by rabbit aorta." American Journal of Physiology. 259. H442-H447 (1990)

[Publications] Hiroshi Shionoiri,Kohsuke Minamisawa,et al.: "Pharmacokinetics and antihypertensive effects of lisinopril in hypertensive patients with noraml and impaired renal function." Journal of Cardiovascular Pharmacology. 16. 564-600 (1990)

[Publications] Takeshi Mizuno,Shigehisa Hirose,et al.: "Radioreceptor assay for atrial natriuretic peptide using purified recptor." Biomedical Research. 11. 29-34 (1990)

[Publications] Hiroshi Shinoiri,Kohichi Sugimoto,et al.: "Clucose and lipid metabolism during longーterm treatment with cilazapril in hypertensive patients with or without impaired glucose metabolism." Journal of Cardiovascular Pharmacology. 15. 933-938 (1990)

[Publications] Mohinder P.Sambhi,et al.: "Selectively enhanced stimulation of DNA synthesis by EGF in vascular smooth muscle cell from SHR." Clinical and Experimental Hypertension. 12 A. 307-316 (1990)

[Publications] Aram V.Chobanian,et al.: "Adaptive and maladaptive responses of the arterial wall to hypertension." Hypertension. 15. 666-674 (1990)

[Publications] Aram V.Chobanian,et al.: "The effect of ACE inthibitors and other antihypertensive drugs on cardiovascular risk factors and atherogenesis." Clinical Cardiology. 13 Suppl.43-48 (1990)

[Publications] Hans R.Brunner,et al.: "The reninーangiotensin system in hypertension." Hospital Practice. 25. 71-81 (1990)

[Publications] Hans R.Brunner,et al.: "Prevention of renal hypertension in the rat by neuropeptide Y." Journal of Hypertension. 8. 21-25 (1990)

[Publications] Hiromi Hagiwara,Shigehisa Hirose,et al: "Properties of rat uterus endothelin receptor site." Biomedical Research. 11. 93-98 (1990)

[Publications] Kohsuke Minamisawa,Hiroshi Shionoiri,et al.: "Depressor effects and pharmacokinetics of single and consecutive doses of delapril in hypertensive patients with normal or impaired renal function." Cardiovascular Drugs and Therapy. 4. 1417-1424 (1990)

[Publications] Masamichi Kozuka,Shigehisa Hirose,Hiromi Hagiwara,et al.: "Endothelin action on rat uterus is inhibited by an inhibitor of protein Kinase C and by inhibitors of the phospolipase A_2ーarachidonic acdーlipoxygenase pathway." Biomedical Research. 11. 287-289 (1990)

[Publications] Hiromi Hagiwara,Shigehisa Hirose,et al.: "Solubilization of endothelin receptors from bovine lung plasma membranes in a nonーaggregated state and estimation of their minimal function sizes." Biochemical and Biophysical Reserch Communications. 172. 576-581 (1990)

[Publications] Aram V.Chobanian,et al.: "Stressーinduced protein in aortic smooth muscle cells and aorta of hypertensive rats." American Journal of Physiology. 258. H1699-H1705 (1990)

[Publications] Hans R.Brunner,et al.: "Treating the individual hypertensive patients:Consideration on dose,sequential monotherapy and drug combination." Journal of Hypertension. 8. 3-11 (1990)

塩之入洋横浜市立大学, 医学部, 講師 (20128599)