Blockade of angiotensin II type-1 receptor increases salt sensitivity in Sprague-Dawley rats
Blockade of angiotensin II type-1 receptor increases salt sensitivity in Sprague-Dawley rats
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DOI：
10.1038/hr.2009.40
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发表时间：
2009-06-01
影响因子：
5.4
通讯作者：
Ito, Sadayoshi
中科院分区：
文献类型：
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作者：
Endo, Satoshi;Mori, Takefumi;Ito, Sadayoshi
本研究确定了血管紧张素 II 1 型 (AT1) 受体在血压盐敏感性中的作用。通过无线电遥测技术监测 Sprague-Dawley 大鼠的平均动脉血压 (MAP)，基线测量后，用 (1) 载体、(2) AT1 受体阻滞剂 (ARB) 奥美沙坦 (OLM，100 nmol kg(-1) h(-1)，皮下注射)、(3) OLM 联合氢氯噻嗪 (HCTZ，40 mg kg(-1) 天(-1)) 治疗，口服），（4）血管紧张素II（AngII，100 ng kg（-1）min（-1），皮下注射）或（5）AngII与OLM。在基线和治疗期的前 7 天，给大鼠喂食含 0.5% 盐的饮食，然后在另外 7 天改为含 8% 盐的饮食。在每个时期结束时将尿液样本收集在代谢笼中。在整个研究过程中，车辆组的 MAP 没有变化。在注射 AngII 的大鼠中，仅当给大鼠喂食 8% 盐饮食时，血压才会升高。当大鼠接受 0.5% 盐饮食时，OLM 和 OLM 与 AngII 显着降低 MAP，但大鼠接受 8% 盐饮食时则不然，这表明 OLM 增强了盐敏感性。与 HCTZ 共同处理降低了 OLM 的盐敏感性。 8% 盐饮食增加了尿中氧化应激标记物的水平，并且单独使用 OLM 或与 HCTZ 联合使用均不会改变氧化应激标记物的水平。然而，OLM 减弱了盐诱导的肾 NAD(P) H（烟酰胺腺嘌呤二核苷酸磷酸）氧化酶活性。这些结果表明 AT1 受体阻断会增加盐敏感性，而利尿剂可以逆转这种情况。我们的结论是，即使在高盐摄入的情况下，OLM 和 HCTZ 也可能成为降低血压的有用组合，而不改变尿氧化应激水平。高血压研究 (2009) 32, 513-519; doi：10.1038/hr.2009.40； 2009 年 5 月 1 日在线发布
This study determined the role of angiotensin II type-1 (AT1) receptor in the salt sensitivity of blood pressure. The mean arterial blood pressure (MAP) of Sprague-Dawley rats was monitored by radio telemetry and, after baseline measurements, rats were treated either with (1) vehicle, (2) AT1 receptor blocker (ARB) olmesartan (OLM, 100 nmol kg(-1) h(-1), subcutaneously), (3) OLM with hydrochlorothiazide (HCTZ, 40 mg kg(-1) day(-1), orally), (4) angiotensin II (AngII, 100 ng kg(-1) min(-1), subcutaneously) or with (5) AngII with OLM. Rats were fed a 0.5% salt diet during the baseline and first 7 days of treatment period, and the diet was then switched to one containing 8% salt for another 7 days. Urinary samples were collected in a metabolic cage at the end of each period. MAP of the vehicle group did not change throughout the study. In AngII-infused rats, BP increased only when rats were fed an 8% salt diet. OLM and OLM with AngII significantly reduced MAP when rats were on a 0.5% salt diet, but not on an 8% salt diet, indicating an enhanced salt sensitivity by OLM. Co-treatment with HCTZ reduced the salt sensitivity of OLM. The urinary level of the oxidative stress marker was increased by an 8% salt diet and was not altered by either OLM alone or in combination with HCTZ. However, OLM attenuated the salt-induced renal NAD(P) H (nicotinamide adenine dinucleotide phosphate) oxidase activity. These results indicate that AT1 receptor blockade increases salt sensitivity, which is reversed by diuretics. We conclude that OLM and HCTZ could be a useful combination for reduction of blood pressure even under high salt intake without changes in urinary oxidative stress levels. Hypertension Research (2009) 32, 513-519; doi: 10.1038/hr.2009.40; published online 1 May 2009