|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1998 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1997 : ¥1,400,000 (Direct Cost : ¥1,400,000)
In the present study, we investigated to clarify the pathophysiological role of angiotensin (Ang) II formation in cardiovascular tissue. It had been known that angioteusin converting enzyme (ACE) converts Aug I to Aug II, whereas recent reports demonstrated that clymase also does. Therefore, to clarify the role of local Aug II formation in human, we needed to choose the experimental species which has Ang II-forming chymase, In the first and second years, we reported that the characterization and the primary structure of moiikey chymase purified and cloned from vascular tissues were very similar to those of human chymase, and that the Aug II concentration and the mRNA levels of ACE and chymase of the atherosclerotic aorta in monkeys fed a high cholesterol diet were increased significantly (FEBS Lett., 412 : 86-90, 1997). Based on these findings, we stiidied the effects of ACE inhibitor and Aug II receptor antagonist in this model. Both ACE inhibitor and Aug II receptor antagonist prevented the development of atherosclerosis (Atherosclerosis 138 : 171-182, 1998). However, both these dnigs did not affect the plasma lipid levels and blood pressure. Although it has been thought that anti-atherosclerotic dnig has need to suppress plasma lipid levels or blood pressure, these findings suggest that increase of Aug II formation in vascular tissues, but not plasma lipid levels and blood pressure, may be relation to development of athcrosclerosis.