Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Hypertens Res. 2013 Oct;36(10):845-51. doi: 10.1038/hr.2013.73. Epub 2013 Jul 18.
Sympathoexcitation has an important role in the pathogenesis of hypertension. Previous studies have demonstrated that nitric oxide (NO) and/or oxidative stress in the brain are important for the regulation of the sympathetic nervous system. We have investigated the role of NO derived from an overexpression of endothelial NO synthase (eNOS) or oxidative stress in the rostral ventrolateral medulla (RVLM), which is known as a vasomotor center in the brainstem, on the regulation of the sympathetic nervous system. Our results indicated that NO derived from an overexpression of eNOS in the RVLM caused sympathoinhibition via an increase in γ-amino butyric acid and that angiotensin II type 1 receptor (AT1R)-induced oxidative stress in the RVLM caused sympathoexcitation. We also demonstrated that oxidative stress in the RVLM caused sympathoexcitation via interactions with NO, effects on the signal transduction or apoptosis of the astrocytes. Furthermore, several orally administered AT1R blockers have been found to cause sympathoinhibition via a reduction in oxidative stress through the blockade of AT1R in the RVLM of hypertensive rats. In conclusion, our studies suggest that the increase in AT1R-induced oxidative stress and/or the decrease in NO in the RVLM mainly cause sympathoexcitation in hypertension.
交感神经兴奋在高血压的发病机制中起重要作用。先前的研究表明，大脑中的一氧化氮（NO）和/或氧化应激对于交感神经系统的调节很重要。我们研究了脑桥中的血管运动中枢——延髓头端腹外侧区（RVLM）中来自内皮型一氧化氮合酶（eNOS）过表达的 NO 或氧化应激在调节交感神经系统中的作用。我们的结果表明，RVLM 中 eNOS 过表达产生的 NO 通过增加γ-氨基丁酸引起交感神经抑制，而 RVLM 中血管紧张素 II 型 1 受体（AT1R）诱导的氧化应激引起交感神经兴奋。我们还证明，RVLM 中的氧化应激通过与 NO 的相互作用、对星形胶质细胞的信号转导或凋亡的影响引起交感神经兴奋。此外，已经发现几种口服 AT1R 阻滞剂通过阻断 RVLM 中的 AT1R 减少氧化应激，从而引起高血压大鼠的交感神经抑制。总之，我们的研究表明，RVLM 中 AT1R 诱导的氧化应激增加和/或 NO 减少主要导致高血压中的交感神经兴奋。
