Reference

Inhibition of angiotensin I-converting enzyme with S 9490: biochemical effects, interspecies differences, and role of sodium diet in hemodynamic effects

Inhibition of angiotensin I-converting enzyme with S 9490: biochemical effects, interspecies differences, and role of sodium diet in hemodynamic effects. Laubie, Michel; Schiavi, Pierre; Vincent, Michel; Schmitt, Henri (Inst. Rech. Servier, Suresnes 92150, Fr.). J. Cardiovasc. Pharmacol., 6(6), 1076-82 (English) 1984. CODEN: JCPCDT. ISSN: 0160-2446. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) S 9780 (I, R = H) [95153-31-4] the diacid form of S 9490 (I; R = Et) [82834-16-0] inhibited guinea pig plasma angiotensin-converting enzyme (ACE) [9015-82-1] by 50% (IC50) at a concn. of 2.4 nM. A Ki of 1.2 nM was obtained for S 9780 (Dixon-Webb plot) with angiotensin I as a substrate. In rabbits, rats, cats, guinea pigs, and dogs, S 9780, MK 422, S 9490, and MK421 decreased, in a dose-dependnet manner, the pressor response to agniotensin I. The rabbit and the rat were the most sensitive species, with ID50 values, resp., of 2.7 and 5.9 mg/kg i.v. for S 9490 and 1.2 and 2.6 mg/kg i.v. for S 9780. S 9490 induced a dose-dependent decrease in serum ACE activity in rabbits (0.6-20 mg/kg i.v.) and guinea pigs (10-100 mg/kg i.v.). In conscious rats and dogs S 9490 (0.03-1 mg/kg, orally) induced a long-lasting inhibition of the angiotensin I-induced pressor response; 40% inhibition was recorded in dogs, 24 h after 1 mg/kg orally. S 9490 (0.03-0.1 mg/kg i.v.) potentiated the increase in femoral blood flow induced by bradykinin injected into the femoral artery of dogs. In anesthetized dogs, mean blood pressure and heart rate were not changed after Na restriction, but the cardiac output was markedly decreased. S 9490 (0.1-1 mg/kg i.v.) decreased mean blood pressure both in Na-restricted and Na-repleted pentobarbital-anesthetized dogs. However, the lowering effect was more pronounced in Na-restricted dogs. S 9490 (3 mg/kg, orally) did not change mean blood pressure in conscious dogs maintained on normal Na diet but decreased mean blood pressure in conscious Na-restricted dogs. Plasma renin [9015-94-5] activity (PRA) and plasma aldosterone [52-39-1] concn. were strongly enhanced in conscious dogs maintained on low-Na diet. S 9490 (3 mg/kg orally) induced a further increase in PRA assocd. with a decrease in plasma aldosterone concn. The degree and duration of ACE inhibition appear to exceed those obtained with MK 421 and MK 422.

Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: the perindopril protection against recurrent stroke study (PROGRESS) CT substudy in Japan

Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: the perindopril protection against recurrent stroke study (PROGRESS) CT substudy in Japan. [Erratum to document cited in CA]. Hasegwa, Yasuhiro; Yamaguchi, Takenori; Omae, Teruo; Woodward, Mark; Chalmers, John (PROGRESS CT Substudy Investigators, Cerebrovascular Division, National Cardiovascular Center, Suita, Japan).Chemicals with cas numbers 82834-16-0 and 26807-65-8 also play role. Hypertension Research, 27(6), 447 (English) 2004 Japanese Society of Hypertension. CODEN: HRESE4. ISSN: 0916-9636. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) On page 154, Appendix, "Tohsei National Hospital: H. Okada, A. Takeda" should be "Tohsei National Hospital: S. Kojima, T. Fuse, Y. Takakubo; Shizuoka City Hospital: R. Waki; Nagoya National Hospital: H. Okada, A. Takeda". .