Osborn John W, Olson Dalay M, Guzman Pilar, Toney Glenn M, Fink Gregory D
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota.
Department of Physiology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Physiol Rep. 2014 Feb 26;2(2):e00245. doi: 10.1002/phy2.245. eCollection 2014 Feb 1.
Hypertension induced by chronic administration of angiotensin II (AngII) is exacerbated by high-salt intake. Previous studies have demonstrated that this salt-sensitive component is due to increased activity of the sympathetic nervous system, suggesting an interaction of plasma AngII with sodium-sensitive regions of the brain. This study tested the hypothesis that the salt-sensitive component of AngII-induced hypertension would be prevented by intracerebroventricular (ICV) administration of the sodium channel/transporter blocker benzamil. Male Sprague Dawley rats were instrumented to measure mean arterial pressure (MAP) by radio telemetry and for ICV administration of benzamil or vehicle and placed in metabolic cages for measurement of sodium and water intake and excretion. In rats consuming a high-salt diet (2.0% NaCl) and treated with ICV vehicle, administration of AngII (150 ng/kg/min, sc) for 13 days increased MAP by ~30 mmHg. ICV administration of benzamil (16 nmol/day) had no effect during the first 5 days of AngII, but returned MAP to control levels by Day 13. There were minimal or no differences between ICV vehicle or benzamil groups in regards to sodium and water balance. A lower dose of ICV benzamil administered ICV at 8 nmol/day had no effect on the MAP response to AngII in rats on a high-salt diet. Finally, in contrast to rats on a high-salt diet, AngII had negligible effects on MAP in rats consuming a low-salt diet (0.1% NaCl) and there were no differences in any variable between ICV benzamil (16 nmol/day) and ICV vehicle-treated groups. We conclude that the salt-sensitive component of AngII-induced hypertension is dependent on benzamil blockable sodium channels or transporters in the brain.
长期给予血管紧张素II（AngII）所诱发的高血压会因高盐摄入而加剧。先前的研究表明，这种盐敏感性成分是由于交感神经系统活性增强所致，这提示血浆AngII与脑内钠敏感区域之间存在相互作用。本研究检验了如下假说：脑室内（ICV）给予钠通道/转运体阻滞剂苄amil可预防AngII诱发高血压中的盐敏感性成分。对雄性斯普拉格-道利大鼠进行仪器植入，以便通过无线电遥测法测量平均动脉压（MAP），并用于ICV给予苄amil或赋形剂，然后将其置于代谢笼中以测量钠和水的摄入与排泄。在食用高盐饮食（2.0% NaCl）并接受ICV赋形剂处理的大鼠中，给予AngII（150 ng/kg/分钟，皮下注射）13天可使MAP升高约30 mmHg。在AngII给药的前5天，ICV给予苄amil（16 nmol/天）没有效果，但到第13天时可使MAP恢复至对照水平。ICV赋形剂组和苄amil组在钠和水平衡方面的差异极小或不存在差异。以8 nmol/天的剂量ICV给予较低剂量的苄amil对食用高盐饮食大鼠的MAP对AngII的反应没有影响。最后，与食用高盐饮食的大鼠相反，AngII对食用低盐饮食（0.1% NaCl）的大鼠的MAP影响可忽略不计，并且ICV苄amil（16 nmol/天）组和ICV赋形剂处理组之间在任何变量上均无差异。我们得出结论，AngII诱发高血压中的盐敏感性成分依赖于脑内可被苄amil阻断的钠通道或转运体。
