Role of afferent and efferent renal nerves in the development of AngII-salt hypertension in rats.
Role of afferent and efferent renal nerves in the development of AngII-salt hypertension in rats.
复制标题
DOI：
10.14814/phy2.13602
复制
发表时间：
2018-03
影响因子：
2.5
通讯作者：
Osborn JW
中科院分区：
文献类型：
--
作者：
Foss JD;Fiege J;Shimizu Y;Collister JP;Mayerhofer T;Wood L;Osborn JW
高血压是世界范围内最主要的可改变的死亡危险因素，但其原因尚不清楚，治疗方法也不理想。导尿管肾去神经支配（RDNX）是一种治疗顽固性高血压的新方法，但其降压作用的机制尚不清楚。我们最近发现RDNX可减轻醋酸氧皮质酮盐高血压，这依赖于肾传入神经的消融术，并与肾脏炎症的减少有关。为了确定这是否与其他盐敏感性高血压模型一样，我们对大鼠进行了完全RDNX （n = 8）、选择性肾传入神经消融（n = 8）或假去神经支配（n = 8）。遥测平均动脉压（MAP）和心率，将大鼠置于代谢笼中测量钠和水平衡。然后对大鼠进行血管紧张素II (AngII) -盐高压（10 ng/kg/min，静脉注射+ 4% NaCl饮食）治疗2周。在研究结束时，用流式细胞术定量肾T细胞浸润。在所有三组中，AngII导致MAP升高~50 mmHg，组间无差异，选择性消融肾传入神经使短暂性心动过缓减弱。钠和水平衡不受AngII - salt处理的影响，各组之间相似。最后，AngII输注与T细胞浸润到肾脏无关，T细胞计数不受去神经支配手术的影响。这些结果表明，大鼠的AngII‐salt高血压与肾脏炎症无关，并且传入和传出肾神经都与该模型无关。
Hypertension is the leading modifiable risk factor for death worldwide, yet the causes remain unclear and treatment remains suboptimal. Catheter‐based renal denervation (RDNX) is a promising new treatment for resistant hypertension, but the mechanisms underlying its antihypertensive effect remain unclear. We recently found that RDNX attenuates deoxycorticosterone acetate‐salt hypertension and that this is dependent on ablation of afferent renal nerves and is associated with decreased renal inflammation. To determine if this is common to other models of salt‐sensitive hypertension, rats underwent complete RDNX (n = 8), selective ablation of afferent renal nerves (n = 8), or sham denervation (n = 8). Mean arterial pressure (MAP) and heart rate were measure by telemetry and rats were housed in metabolic cages for measurement of sodium and water balance. Rats were then subjected to angiotensin II (AngII)‐salt hypertension (10 ng/kg/min, intravenous + 4% NaCl diet) for 2 weeks. At the end of the study, renal T‐cell infiltration was quantified by flow cytometry. AngII resulted in an increase in MAP of ~50 mmHg in all three groups with no between group differences, and a transient bradycardia that was blunted by selective ablation of afferent renal nerves. Sodium and water balance were unaffected by AngII‐salt treatment and similar between groups. Lastly, AngII infusion was not associated with T‐cell infiltration into the kidneys, and T‐cell counts were unaffected by the denervation procedures. These results suggest that AngII‐salt hypertension in the rat is not associated with renal inflammation and that neither afferent nor efferent renal nerves contribute to this model.