Contribution of angiotensin converting enzyme gene polymorphism to the action of angiotensin II receptor antagonist (CS-866)

Akinori Urae, Mitsuko Okada, Ichiro Ieiri, Shun Higuchi, Masafumi Hisaoka, Masazo Tajima, Toshio Ogihara, Shigeyuki Nakano

Research output: Contribution to journalArticle

Abstract

An insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene has been reported to affect the activity of ACE. This study was conducted to investigate the relationship between the action of the angiotensin II receptor antagonist CS-866 and the insertion/deletion (I/D) polymorphism of the ACE gene in Japanese healthy subjects. The effects of a single oral dose of CS-866 16 mg on blood pressure (BP) and pulse rate in relation to the ACE genotype were studied in 12 healthy men, 7 with the II genotype and 5 with the DD genotype. The pharmacodynamics of CS-866 in relation to the ACE genotype was evaluated. The effect of CS-866 on the plasma renin-angiotensin system was determined. The plasma levels of angiotensin II were significantly higher in the DD genotype than the II genotype before the administration of CS-866. The insertion/deletion polymorphism did not change any pharmacokinetic parameters of CS-866 in plasma. BP in the supine position decreased with the administration of CS-866, while the pulse rate increased. The increase in plasma levels of angiotensin II following administration of CS-866 was associated with the potency of the action of CS-866. The BP-lowering action of CS-866 was greater in the DD genotype subjects than in II genotype subjects. Postural change amplified this genetic difference. The increase in the levels of angiotensin II following administration of CS-866 appears to be closely related to the antihypertensive action of CS-866. Higher activity of ACE in the subjects with the DD genotype might potentiate the action of CS-866, probably intensifying the rise in the levels of angiotensin II.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalJapanese Journal of Clinical Pharmacology and Therapeutics
Volume33
Issue number2
DOIs
Publication statusPublished - Jan 1 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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