Clinical and pharmacotherapeutic relevance of the double-chain domain of the angiotensin II type 1 receptor blocker olmesartan.
Clinical and pharmacotherapeutic relevance of the double-chain domain of the angiotensin II type 1 receptor blocker olmesartan.
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DOI：
10.3109/10641960903254430
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Saku K
中科院分区：
文献类型：
--
作者：
Kiya Y;Miura S;Fujino M;Imaizumi S;Karnik SS;Saku K
我们以前报道，血管紧张素II 1型（AT 1）受体阻滞剂（ARB）奥美沙坦有两个重要的相互作用，引起反激动（IA）。我们将这些相互作用称为“双链结构域（DCD）”。由于奥美沙坦的临床药理学相关性尚不清楚，我们在大鼠和人体中检查了这些作用。我们分析了Dahl盐敏感性高血压大鼠肾功能不全晚期的影响（研究1）。大鼠从9周龄开始喂食高盐饮食，并在16 - 21周龄时随机分配至3种治疗方案：奥美沙坦（2 mg/kg/天）+DCD、一种与奥美沙坦相关的化合物（6 mg/kg/天，R-239470）不含DCD或安慰剂。我们还比较了奥美沙坦与其他ARB在原发性高血压患者中的降压作用（研究2）。本研究招募了30例接受奥美沙坦以外ARB治疗的原发性高血压门诊患者。我们的方案得到了医院伦理委员会的批准，并在从奥美沙坦以外的ARB转换为奥美沙坦前12周获得了所有患者的知情同意书。在研究1中，奥美沙坦在21周龄时对尿蛋白排泄与肌酐的比值产生了更显著的抑制作用，而三组中血压没有降低。在研究2中，奥美沙坦的降压作用显著强于不含DCD的其他ARB。奥美沙坦的这些累加效应可能是由于DCD。
We previously reported that the angiotensin II type 1 (AT1) receptor blocker (ARB) olmesartan has two important interactions to evoke inverse agonism (IA). We refer to these interactions as the “double-chain domain (DCD).” Since the clinical pharmacotherapeutic relevance of olmesartan is still unclear, we examined these effects in rats and humans. We analyzed the effects at an advanced stage of renal insufficiency in Dahl salt-sensitive hypertensive rats (Study 1). Rats were fed a high-salt diet from age 9 weeks and arbitrarily assigned to three treatment regimens at age 16 to 21 weeks: olmesartan (2 mg/kg/day) with DCD, a compound related to olmesartan without DCD (6 mg/kg/day, R-239470) or placebo. We also compared the depressor effects of olmesartan to those of other ARBs in patients with essential hypertension (Study 2). Thirty essential hypertensive outpatients who had been receiving ARBs other than olmesartan were recruited for this study. Our protocol was approved by the hospital ethics committee and informed consent was obtained from all patients 12 weeks prior to switching from ARBs other than olmesartan to olmesartan. In Study 1, olmesartan induced a more prominent suppression of the ratio of urinary protein excretion to creatinine at age 21 weeks without lowering blood pressure among the three groups. In Study 2, the depressor effect of olmesartan was significantly stronger than those of other ARBs, which do not contain the DCD. These additive effects by olmesartan may be due to DCD.
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DOI：
10.1073/pnas.86.19.7321
发表时间：
1989-10-01
影响因子：
11.1
作者：
COSTA, T;HERZ, A
通讯作者：
HERZ, A
影响因子：
37.8
作者：
McKelvie, RS;Yusuf, S;Pogue, J
通讯作者：
Pogue, J
影响因子：
5.4
作者：
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通讯作者：
Ogihara, Toshio
影响因子：
21.3
作者：
Zou, YZ;Akazawa, H;Komuro, I
通讯作者：
Komuro, I
DOI：
10.1097/01.asn.0000027871.86296.92
发表时间：
2002-09-01
影响因子：
13.6
作者：
De Leeuw, PW;Thijs, L;Staessen, JA
通讯作者：
Staessen, JA