Activation of the renin–angiotensin system in α-calcitonin gene-related peptide/calcitonin gene knockout mice
Activation of the renin–angiotensin system in α-calcitonin gene-related peptide/calcitonin gene knockout mice
复制标题
DOI：
10.1097/01.hjh.0000125409.50839.f1
复制
发表时间：
2004-07
影响因子：
4.9
通讯作者：
Jianping Li;Huawei Zhao;S. Supowit;D. DiPette;Donna H. Wang
中科院分区：
文献类型：
--
作者：
Jianping Li;Huawei Zhao;S. Supowit;D. DiPette;Donna H. Wang
目的探讨α-降钙素基因相关肽（α-CGRP）基因敲除小鼠循环或组织中的肾素-血管紧张素系统（RAS）活性升高，从而导致血压升高的可能性。设计和方法研究了3至6个月大的雄性αCGRP/降钙素基因敲除小鼠和野生型对照小鼠。平均动脉压（MAP）及其对血管紧张素II 1型（AT 1）受体阻断剂氯沙坦（3 mg/kg静脉注射）的反应在清醒、无限制的基因敲除小鼠和野生型小鼠中测定。分别采用放射免疫法和免疫印迹法测定血浆肾素活性（PRA）和组织中AT 1受体蛋白含量。结果基因敲除小鼠的基础MAP和PRA显著高于野生型小鼠。与此相反，AT 1受体的含量在肾髓质显着减少敲除小鼠与野生型小鼠相比。在敲除和野生型小鼠中，肾皮质和肠系膜阻力动脉中的AT 1受体含量没有差异。与野生型小鼠相比，氯沙坦在基因敲除小鼠中产生了显著的MAP降低。结论αCGRP/降钙素基因敲除小鼠循环RAS活性升高，而组织AT 1受体表达无明显变化，可能是该模型血压升高的原因之一。在这些动物的整个发育阶段，在不存在αCGRP的情况下，循环RAS活性增加的机制仍有待确定。
Objective To test the hypotheses that circulating or tissue renin–angiotensin system (RAS) activity is increased in α-calcitonin gene-related peptide (αCGRP) knockout mice, and that this contributes to the increased blood pressure in these mice. Design and methods Three- to six-month-old male αCGRP/calcitonin knockout mice and wild-type controls were studied. Mean arterial pressure (MAP) and its response to an angiotensin II type 1 (AT1) receptor blocker, losartan (3 mg/kg intravenously), were determined in conscious, unrestrained knockout mice and wild-type mice. Radioimmunoassay and western blot were used, respectively, to determine plasma renin activity (PRA) and AT1 receptor protein content in tissues. Results Basal MAP and PRA were significantly greater in the knockout mice than in the wild-type mice. In contrast, AT1 receptor content in the renal medulla was significantly decreased in the knockout mice compared with that in wild-type mice. AT1 receptor content in the renal cortex and mesenteric resistance arteries was not different in the knockout and wild-type mice. Losartan produced a significant decrease in MAP in the knockout mice compared with that in wild-type mice. Conclusion Activity of the circulating RAS, but not tissue AT1 receptor expression, is increased in αCGRP/calcitonin knockout mice, which may contribute to the increase in blood pressure in this mouse model. The mechanism(s) responsible for the increased activity of the circulating RAS in the absence of αCGRP throughout the developmental stages of these animals remains to be determined.