Studies on angiotensin I converting enzyme (ACE): Inhibitory effect of imidapril, a novel ACE inhibitor (II). Inhibition of various tissue ACEs ex vivo.

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  • HASHIMOTO Yoshikatsu
    Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd.
  • KUBO Masami
    Research Laboratory of Applied Biochemistry, Tanabe Seiyaku Co., Ltd.
  • SUGAYA Takeshi
    Research Laboratory of Applied Biochemistry, Tanabe Seiyaku Co., Ltd.
  • MINOBE Satoshi
    Research Laboratory of Applied Biochemistry, Tanabe Seiyaku Co., Ltd.
  • WATANABE Taizo
    Research Laboratory of Applied Biochemistry, Tanabe Seiyaku Co., Ltd.
  • YAMAMURA Michio
    Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd.
  • MATSUOKA Yuzo
    Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd.

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Other Title
  • ＩｍｉｄａｐｒｉｌのアンジオテンシンＩ変換酵素（ＡＣＥ）阻害作用に関する研究（ＩＩ）　ｅｘ　ｖｉｖｏにおける各種組織ＡＣＥに対する作用
  • Imidapril ノ アンジオテンシン 1 ヘンカン コウソ ACE ソガイ
  • Inhibition of various tissue ACEs ex vivo.
  • ―ex vivoにおける各種組織ACEに対する作用―

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The antihypertensive mechanism of imidapril was investigated in relation to its inhibition of ACE activities in the serum, thoracic-abdominal aorta, lung, kidney, heart and brain from adult spontaneously hypertensive rats (SHRs). In comparison with normotensive rats (NTRs), the ACE activities in the aorta, heart, brain and lung were higher, while those in the serum and kidney were considerably lower. Imidapril (2 mg/kg) showed remarkable inhibitions within 6 hr in all tissues, except for the brain, after a single oral administration. Consecutive administration of imidapril (2 mg/kg/day) for 30 days produced inhibitions in all tissues. The inhibitions in the serum, aorta and lung were greater, and the duration of inhibition in the aorta, brain and lung were longer. Blood pressure declined gradually until 6 hr, and the reductions were significant at 24 hr after the single and chronic administrations. Imidapril (0.5 mg/kg, ineffective on normal blood pressure) inhibited ACE activities in NTRs similarly. Enalapril at the same dose exhibited less ACE inhibition and antihypertension. These results suggest that the ACE inhibition in the serum, lung and aorta by imidapril correlate with the antihypertension in SHRs; especially, the lung and vascular ACE inhibitions play an important role in the duration of antihypertension in SHRs.

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