| Project/Area Number |
62304041
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
MASUYAMA Yoshiaki Wakayama Medical College, Medicine, Professor, 医学部, 教授 (30089164)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Shoichi Niigata University, Medicine, Professor, 医学部, 教授 (60013869)
FUJITA Takuo Kobe University, Medicine, Professor, 医学部, 教授 (30009964)
YOSHINAGA Kaoru Tohoku University, Medicine, Professor, 医学部, 教授 (00004557)
HIDAKA Hiroyoshi Nagoya University, Medicine, Professor, 医学部, 教授 (80100171)
OGATA Etsuro University of Tokyo, Medicine, Professor, 医学部, 教授 (70013761)
岸 浩一郎 (岸浩 一郎) 自治医科大学, 医学部, 教授 (50161435)
山下 亀次郎 筑波大学, 臨床医学系, 教授 (80015982)
猿田 享男 慶応義塾大学, 医学部, 教授 (70051571)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 1989: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1987: ¥15,000,000 (Direct Cost: ¥15,000,000)
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| Keywords | Hypertension / Calcium / Myosin light chain / Protein kinase C / Inositol phosphate / Endothelin / Ca-ATPase / Vascular responsiveness / キナ-ゼII / Ca ATPase / プロスタサイクリン / ナトリウム / 高血圧自然発症ラット / 本態性高血圧 / Ca / Mg / ミオンシン軽鎖 / Cキナーゼ / イノシトールリン脂質 / Ca-ATPaseブラジキニン / プロスタグランディン / 血清由来成長因子 / ビタミンD / 本熊性高血圧 / カルモデュリン |
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| Research Abstract |
In the present study, the roles of calcium in the pathogenesis of hypertension, the alteration of calcium metabolism and the antihypertensive effect of calcium supplementation were investigated and following results were obtained.
Phosphorylation of myosin light chain kinase(MLCK) was linked with vascular contraction. Kinase II contributed to the regulation of blood pressure in the central nervous system(Hidaka). Receptor-mediated vascular contraction was mediated by the formation of IP_3 and phosphorylation of MLCK. Protein kinase C inhibited Ca-mobilization from the intracellular Ca store induced by IP_3- Ca-storage mechanism existed in the intracellular Ca store sites(Fujita). G-kinase and C-kinase stimulated Ca^<2+>-ATPase in the vascular cell membrane(Imai). Angiotensin II and vasopressin stimulated the IP_3 formation and mobilized Ca from intracellular Ca store sites. These vasoactive peptides were also activated phospholipase A_2 which stimulated the PGI_2 formation and suppresse
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d the vascular contraction(Yoshinaga). Endothelin produced rapid increase of intracellular free Ca concentration by Ca-mobilization followed by continuous slight increase of free Ca by Ca- influx(Yamashita). Spontaneously hypertensive rats(SHR) showed increased calpain activity In the mesenteric artery(Kishi). Calcium supplementation reduced blood pressure in SHR, Dahl-salt sensitive rats and two-kidney, one clip hypertension. These effects were caused by suppression of vascular responsiveness(Saruta). Calcium supplementation reduced pressor response of mesenteric artery and intracellular free calcium concentration and normalized membrane fluidity of erythrocyte in SOR(Masuyama). Renin-angiotensin system was correlated with antihypertensive effects induced by calcium loading in SIIR and Dahl-salt sensitive rats. In the patients with essential hypertension, metabolism of vitamin D was altered and this alteration contributed to the increase of blood pressure by salt loading.
These results clarify the calcium-mediated intracellular signaling system in the vascular smooth muscle cells, alteration of calcium metabolism in hypertension and the antihypertensive mechanisms of calcium supplementation. Less
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