| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
The renin-angiotensin-aldosterone system has been known as one of the most potent controlling system of the blood pressure. The circulating renin-angiotensin system has been thought to be the main source of angiotensins. However, recently there are several reports that the major sites of the formation of angiotensin are peripheral tissues including brain,kidney,adrenal gland,and arterial wall. Full sets of the renin-angiotensin system, i.e.,renin, converting enzyme and renin substrate are reported to exist in those tissues.
The purpose of the study was to demonstrate the generation and metabolism of angiotensins using the hindquarter vascular perfusion system and to clarify whether there exists the alternate pathway of angiotensin formation in addition to the classical renin-converting enzyme cascade. Following results were obtained;
(1)Hindquarter perfusion system was establishid.
(2)Synthetic angiotensin II(10(micrn)g/20ml) was perfused in the perfusing system and angiotensin II was extracted from the perfusate and about 20 % of angiotensin II was recovered.
(3)When angiotensin I(100 ng/20 ml) was perfused in the system, about 20 % of angiotensin II was generated. Formation of angiot ensin II was partially inhibited by captopril,a potent converting enzyme inhibitor and more strongly inhibited by captopril plus trasylol,a trypsin-kallikrein inhibitor.
(4)When synthetic tridecapeptide renin substrate(10(micrn)g/20 ml) was perfused,angiotensin I and II were recovered from the perfusate. Although captopril could not inhibit the generation of angiotensin II.
(5)To check whether the immunoreactive angiotensin II is the octapeptide angiotensin II was also conducted after high performance liquid chromatography.
From these results,the vasculature per se plays roles to generate and metabolize angiotensins. In addition, these results also suggest that some enzymes other thana classical reninconverting enzyme system might perticipate in thegeneration or conversion of angiotensins.
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