A-10. アンジオテンシンII拮抗性ペプチドの臨床応用

• Published in: Proceedings of the Symposium on Chemical Physiology and Pathology Vol. 17; pp. 49 - 53
• Main Authors: 中丸, 光昭, 萬代, 隆, 波多, 丈, 三上, 洋, 熊原, 雄一, 荻原, 俊男
• Format: Journal Article
• Language: Japanese
• Published: 一般社団法人 日本臨床化学会 1978; Japan Society of Clinical Chemistry
• ISSN: 0386-3417; 2187-4085
• DOI: 10.14921/jscc1971a.17.0_49

Two angiotensin H analogues are now available in clinical study. Comparative studies of the antagonistic potency and the agonisic effect between these two analogues, i. e., [1-Sarcosine, 8-Isoleusine] angiotensin II and [1-Sarcosine, 8-Alanine] angiotensin II, were done in normal subjects on various sodium balances and in hypertensives on sodium depletion. Both analogues had an agonistic pressor effect in normals. There was found agonistic effects in both compounds not only on blood pressure, but also renin and aldosterone secretion and creatinine clearance in normal subjects on regular diet. The agonistic pressor effects changed with different sodium balances. In low sodium phase, these pressor effects were minimized. Agonistic effect of [1-Sar, 8-Ile] A II was greater than that of [1-Sar, 8-Ala] A II in all sodium balances. The antagonistic effects of both compounds were also varied by changing sodium balance, being greatest in low sodium phase. In hypertensives on sodium depletion, blood pressure responses (δBP) to these A II analogues were significantly correlated (r=0.8, n=20). These results indicate that pretreatment of sodium depletion is necessary to prevent the side effects caused by agonistic pressor effects of these analogues, and also to predict renin dependency in hypertensive patiens efficiently.Results of clinical application of [1-Sar, 8-Ile] A II are as follows:(1) This compound showed a pressor response in low reninemic state, and a depressor response in some cases with high plasma renin activity (PRA). There was a negative correlation between pre-infusion PRA and change in blood pressure following the infusion of this compound. In most high reninemic patients, a depressor response was observed after sodium depletion.(2) In subjects with Cushing's syndrome and pheochromocytoma, a marked pressor response was observed.(3)[1-Sar, 8-Ile] A II reduced blood pressure in a part of normotensive secondary aldosteronism, such as liver cirrhosis with ascites, Bartter's syndrome, congestive heart failure and renal tubular acidosis, and a case of Addison's disease.(4) Subjects taking oral contraceptives with or without hypertension showed no reduction of blood pressure in our limited study. These results indicate that R-A-A system play an important role in the maintenance of normal blood pressure in normotensive secondary aldosteronism and of high blood pressure in a part of high reninemic hypertension.Application of these A II inhibiting analogues should be useful for the understanding the role of R-A-A system in physiological and pathophysiological conditions in human.