1992 Fiscal Year Final Research Report Summary
Interaction of Angiotensin II and kinin on the formation of atherosclerotic lesion
| Project/Area Number |
02454264
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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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 | Fukuoka University |
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Principal Investigator |
ARAKAWA Kikuo Fukuoka University School of Medicine, Professor, 医学部, 教授 (90078783)
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| Co-Investigator(Kenkyū-buntansha) |
SASAGURI Manabu Fukuoka University School of Medicine, Lecturer, 医学部, 講師 (00178675)
IDEISHI Munehito Fukuoka University School of Medicine, Lecturer, 医学部, 講師 (20131807)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Angiotensin / bradykinin / endothelial cell / smooth muscle cell / chymostatin / 増殖因子 |
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| Research Abstract |
1. Vascular endothelial cells and smooth muscle cells were obtained from porcine aorta. Effects of angiotensin II and bradykinin on intracellular Ca concentration, expression of protooncogene c-fos and proliferations of these cells were examined.
(1)Smooth muscle cell proliferation measured by DNA systhesis were not altered by the addition of angiotensin II or bradykinin. In addition, angiotensin converting enzyme inhibitor and angiotensin antagonist were also not effective. On the contrary, Co-culture with confluent endothelial cells or the addition of post culture medium of endothelial cells stimulated the growth of smooth muscle cells. The endothelial cell-derived smooth muscle cellgrowth factor was inactivated totally by heat treatment and partially by trypsinization. The molecular weight of the factor was estimated as 50-100KDa by a filtration method. These suggested the factor was distinct from known growth factors PDGF or FGF.
(2)Intra cellular free Ca concentration was measure by Fura-2 method. Both angiotenisn II and bradykinin raised intracellular free Ca concentration of smooth muscle cells. Repetitive application of angiotensin II showed well known tachyphylaxis. However, pretreatment with bradykinin did not interfere with the effect of angiotensin II. Endothelial cells in this experiment did not respond to bradykinin.
(3)Protooncogene c-fos expression was determined by Nortehern blot analysis. Both angiotenisn II and bradykinin stimulated c-fos expression.
2. Clinical study on the interaction of angiotensin II and bradykinin We have previously reported the alternate angiotensin II forming pathway, kinin-tensisn system. In which, serine protease such as trypsin and kallikrein forms both kinins in an alkaline condition and angiotensin II in an acidic condition. The operation of the pathway in humans has not confirmed.
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