Pharmacology of CS-866, a novel nonpeptide angiotensin II receptor antagonist

Mizuno, Makoto; Sada, Toshio; Ikeda, Masahiro; Fukuda, Norio; Miyamoto, Masaaki; Yanagisawa, Hideyoshi; Koike, Hiroyuki

doi:10.1016/0014-2999(95)00401-6

Cited by 146 publications

(125 citation statements)

References 10 publications

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“…Drugs CS-866 (20), a selective non-peptide angiotensin AT1 receptor antagonist, and temocapril hydrochloride (21), an angiotensin-converting enzyme (ACE) inhibitor, were synthesized by Sankyo Co., Ltd. (Tokyo, Japan). These drugs were suspended in 0.5% carboxymethylcellulose (CMC).…”

Section: Methodsmentioning

confidence: 99%

Effects of Angiotensin AT1 Receptor Antagonist on Volume Overload-Induced Cardiac Gene Expression in Rats.

et al. 1997

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The present study was undertaken to examine the effects of volume overload on cardiac gene expression and the possible role of angiotensin ATl receptor in such expression. Cardiac volume overload was prepared by abdominal aortocaval shunt in rats. Rats with aortocaval shunt were treated with 1) vehicle, 2) an angiotensin ATi receptor antagonist, CS-866 (10 mg/kg/d), or 3) an angiotensin-converting enzyme inhibitor, temocapril (10 mg/kg/d), for 7 days. Cardiac tissue mRNA was measured by Northern blot analysis with specific probes. Aortocaval shunt not only caused cardiac hypertrophy but also upregulated the gene expression of atrial natriuretic polypeptide, collagen III, and downregulated Cat+. ATPase expression in the left ventricle. These changes were prevented by treatment with CS-866, while temocapril failed to normalize left ventricular Cat+-ATPase expression. Unlike the left ventricle, the significant downregulation of a-myosin heavy chain and transforming growth factor-i93 by aortocaval shunt was observed in the right ventricle, and CS-866 normalized this decreased expression of transforming growth factor-/93. The left and right atria showed increased expression of collagen type I as well as of collagen type III and atrial natriuretic polypeptide, and these increases were more effectively prevented by CS-866 than by temocapril. Thus, the effects of cardiac volume overload on cardiac performance-related gene expression differ between the ventricles and atria. Our results suggest that ATi receptor partially contributed to volume overload-induced changes in cardiac gene expression and that ATi receptor antagonists and angiotensin-converting enzyme inhibitors have different effects in this model of cardiac hypertrophy. (Hypertens Res 1997; 20: 133-142)

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Section: Methodsmentioning

confidence: 99%

Effects of Angiotensin AT1 Receptor Antagonist on Volume Overload-Induced Cardiac Gene Expression in Rats.

et al. 1997

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“…Experiments were performed for 1 h. Similarly, AII 10 − 7 mol/L was inoculated onto HUVEC after pretreatment with fullerene at the concentrations of 0.1 μmol/L, 1 μmol/L, and 10 μmol/L, as described above, and left for 1 h. The dose-dependency of AII was also monitored for intracellular ROS production. After referring to previous reports of in vitro studies, RNH was used at 20 μmol/L concentration (36)(37)(38). The experiment was repeated four times.…”

Section: Fluorescence Measurement Of Intracellular Ros and Peroxynitrmentioning

confidence: 99%

A Water-Soluble Fullerene Vesicle Alleviates Angiotensin II-Induced Oxidative Stress in Human Umbilical Venous Endothelial Cells

et al. 2008

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“…21 Also, the duration of the inhibitory effect of RNH 6270 was longer than that of EXP 3174 (90 vs 60 min, respectively).…”

Section: Pharmacodynamic Profilementioning

confidence: 92%

“…15,[21][22][23] In addition, in human volunteers, administration of olmesartan medoxomil 10-40 mg/day blocked the hypertensive response to exogenously administered angiotensin I by greater than 75% for 24 h, compared to controls. 5 …”

Section: Pharmacodynamic Profilementioning

confidence: 95%

Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update

2007

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Olmesartan medoxomil is an angiotensin II (Ang II) receptor blocker (ARB) that has been approved by the US Food and Drug Administration (FDA) for the treatment of hypertension. It is a prodrug that is hydrolysed in the gut into its active metabolite, olmesartan (RNH-6270). Olmesartan is highly selective for the Ang II type 1 receptor (AT1) to which it binds completely and insurmountably and has very little affinity for the other receptor subtypes AT2 and AT4. After oral administration, in animals and humans, it achieves a maximal blood drug concentration within a maximal time of approximately 2 h. It is then slowly eliminated in the urine and faeces. His half-life is approximately 13 h, which makes it suitable for once-daily administration. Olmesartan medoxomil given orally in single daily doses of 20-40 mg has demonstrated significant blood pressure (BP) lowering effects in hypertensive patients. A medline search for the preparation of this manuscript was conducted and revealed 128 references, from 2000 to 2007. Of these, only 16 well-designed prospective clinical trials were selected. The remaining were either animal studies, reviews or studies in progress. In well-designed clinical trials, olmesartan medoxomil has demonstrated similar antihypertensive actions to the other antihypertensive drugs, as well as other members of its class given the highest recommended doses. In addition, the BP lowering effect of olmesartan, like the other members of its class, is greatly enhanced in combination with a diuretic. Its safety profile is similar to the other ARBs and no different than placebo.

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Pharmacology of CS-866, a novel nonpeptide angiotensin II receptor antagonist

Cited by 146 publications

References 10 publications

Effects of Angiotensin AT1 Receptor Antagonist on Volume Overload-Induced Cardiac Gene Expression in Rats.

Effects of Angiotensin AT1 Receptor Antagonist on Volume Overload-Induced Cardiac Gene Expression in Rats.

A Water-Soluble Fullerene Vesicle Alleviates Angiotensin II-Induced Oxidative Stress in Human Umbilical Venous Endothelial Cells

Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update

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