Reversal of genetic salt-sensitive hypertension by targeted sympathetic ablation.
Reversal of genetic salt-sensitive hypertension by targeted sympathetic ablation.
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DOI：
10.1161/hypertensionaha.111.00474
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Osborn JW
中科院分区：
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作者：
Foss JD;Fink GD;Osborn JW
交感神经系统在某些形式的人类高血压以及Dahl盐敏感高血压大鼠模型中起重要作用；然而，所涉及的同情目标仍不清楚。为了解决这个问题，我们通过对高血压达尔大鼠进行假手术（n = 10）或有针对性地切除肾神经（肾去神经，n = 11）、内脏神经（腹腔神经节切除术，n = 11）或同时切除肾和内脏神经（n = 11）来研究肾和内脏神经在达尔高血压中的作用。平均动脉压从0.1%氯化钠饮食时的~120 mmHg增加到4.0%氯化钠饮食三周后的~140 mmHg。在这一点上，大鼠接受了假或有针对性的交感神经消融术。治疗4周后，肾去神经组（150.4±10.4）和腹腔神经节切除组（147.0±6.1）的平均动脉压低于假手术组（165.0±3.7），两组的平均动脉压更低（128.4±6.6）。假手术大鼠和肾去神经大鼠的心率和体液平衡无差异；然而，接受腹腔神经节切除术或两次消融的大鼠在治疗后表现出明显的心动过速以及钠和水潴留。这些数据表明，靶向交感神经消融是治疗Dahl大鼠高血压的有效方法，肾脏和内脏血管床在该模型中都是交感神经系统独立的重要靶点。
The sympathetic nervous system plays an important role in some forms of human hypertension as well as the Dahl salt-sensitive rat model of hypertension; however, the sympathetic targets involved remain unclear. To address this, we examined the role of the renal and splanchnic sympathetic nerves in Dahl hypertension by performing either sham surgery (n = 10) or targeted sympathetic ablation of the renal nerves (renal denervation, n = 11), the splanchnic nerves (celiac ganglionectomy, n = 11) or both renal and splanchnic nerves (n = 11) in hypertensive Dahl rats. Mean arterial pressure increased from ~120 mmHg while on a 0.1% sodium chloride diet, to ~140 mmHg after being fed a 4.0% sodium chloride diet for three weeks. At that point rats underwent sham or targeted sympathetic ablation. Four weeks after treatment, mean arterial pressure was lower in renal denervated (150.4 ± 10.4) and celiac ganglionectomized (147.0 ± 6.1) rats compared to sham rats (165.0 ± 3.7), and even lower in rats that underwent both ablations (128.4 ± 6.6). There were no differences in heart rate or fluid balance between sham and renal denervated rats; however, rats that underwent either celiac ganglionectomy or both ablations exhibited marked tachycardia as well as sodium and water retention following treatment. These data suggest that targeted sympathetic ablation is an effective treatment for established hypertension in the Dahl rat and that the kidneys and the splanchnic vascular bed are both independently important targets of the sympathetic nervous system in this model.