Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension
Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension
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DOI：
10.1152/ajpregu.00783.2007
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发表时间：
2008-11-01
影响因子：
2.8
通讯作者：
Fink, Gregory
中科院分区：
文献类型：
--
作者：
Li, Melissa;Dai, Xiaoling;Fink, Gregory
内皮素(ET)B型受体(ETBR)在多种组织中表达，并根据其位置的不同发挥不同的功能。ETBR介导内皮依赖的血管扩张、循环ET的清除和利尿作用；所有这些都应该导致动脉血压的下降。然而，我们最近发现，使用选择性激动剂沙拉福毒素6c(S6c)的大鼠ETBR的慢性激活会导致持续性高血压。我们提出，这种效应的一个机制是电容管的收缩。目前的研究是为了确定S6c高血压是否由反应性氧自由基(ROS)的生成增加和/或交感神经系统的激活引起。动物模型为雄性SD大鼠连续5天注射S6c。经S6c治疗的高血压大鼠动脉和静脉超氧阴离子水平无明显变化。然而，S6c处理的大鼠的交感神经节中超氧化物歧化水平升高。此外，动物服用S6c的时间越长，神经节中的超氧阴离子含量就越高。抗氧化剂Tempoll可降低S6c诱导的高血压，降低神经节内超氧化物歧化水平。在S6c治疗的大鼠中，急性神经节阻断对血压的降低作用比在赋形剂治疗的大鼠中更大。虽然血浆去甲肾上腺素水平在S6c高血压患者中没有增加，但外科手术切除为内脏器官提供大部分交感神经支配的腹神经节丛显著地减轻了高血压的发展。结果提示，S6c诱发的高血压部分是由椎前交感神经节氧化应激增加引起的内脏器官交感兴奋所致。
Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.