Faculty of Medicine, University of Ipatinga IMES, Minas Gerais, Brasil.
Eur J Pharmacol. 2012 Aug 15;689(1-3):147-53. doi: 10.1016/j.ejphar.2012.05.025. Epub 2012 May 28.
The G protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor and is associated with angiotensin-(1-7) signaling. We investigated the effect of Mas-deficiency on blood pressure regulation under physiological conditions and salt load using radiotelemetry. Mas-knockout mice and their wild-type controls received a telemetry implant in the carotid artery. One week after surgery, animals were monitored for 3 days receiving normal diet (0.6% NaCl) followed by one-week high-salt diet (8% NaCl). Under same high-salt diet, another set of mice was placed in individual metabolic cages for 4 days. Basal mean arterial pressure, heart rate and locomotor activity displayed normal day-night rhythm in Mas-deficient mice. Mas-knockout mice were normotensive. High dietary NaCl ingestion did not alter heart rate or locomotor activity in both groups, but significantly increased night time mean arterial pressure in control mice whereas this increase was blunted in Mas-deficient mice. Baseline food and water intake and urine osmolality were not different between both genotypes. Under high-salt diet, water consumption and food intake were equally increased in wild-type controls and Mas-knockout, but urinary electrolytes and osmolality were significantly higher in Mas-knockout. Taken together, basal hemodynamic parameters are unchanged in Mas-knockout mice. In contrast to wild-type controls, telemetric mean arterial pressure measurement revealed salt resistance in Mas-deficient animals, probably due to their higher urinary NaCl excretion. This is the first direct proof that Mas blockade might be a new option in the treatment of salt-sensitive hypertension.
G 蛋白偶联受体 Mas 是血管紧张素 II 型 1 受体的生理性拮抗剂，与血管紧张素-(1-7)信号有关。我们使用无线电遥测技术研究了 Mas 缺乏对生理条件下和盐负荷下血压调节的影响。Mas 敲除小鼠及其野生型对照动物接受颈动脉植入的遥测装置。手术后一周，动物接受正常饮食（0.6%NaCl）监测 3 天，然后接受一周高盐饮食（8%NaCl）。在相同的高盐饮食下，另一组小鼠被放置在单独的代谢笼中 4 天。Mas 缺陷小鼠的基础平均动脉压、心率和运动活性显示出正常的昼夜节律。Mas 敲除小鼠血压正常。高盐饮食摄入并未改变两组动物的心率或运动活性，但显著增加了对照组动物的夜间平均动脉压，而这种增加在 Mas 敲除小鼠中减弱。两组基因型之间的基础食物和水摄入量以及尿渗透压没有差异。在高盐饮食下，野生型对照和 Mas 敲除小鼠的水摄入量和食物摄入量同样增加，但 Mas 敲除小鼠的尿电解质和渗透压显著升高。总之，Mas 敲除小鼠的基础血液动力学参数没有变化。与野生型对照相比，遥测平均动脉压测量显示 Mas 缺陷动物对盐有抗性，可能是由于它们的尿 NaCl 排泄量增加。这是 Mas 阻断可能成为治疗盐敏感型高血压的新选择的第一个直接证据。
