在清醒大鼠中，神经元型一氧化氮合酶（nNOS）在延髓中在反复给予乙醇引起的心动过速中的作用。
Role of neuronal nitric oxide synthase (nNOS) at medulla in tachycardia induced by repeated administration of ethanol in conscious rats.
机构信息
Master and PhD Programs in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien, Taiwan.
Department of Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan.
出版信息
J Biomed Sci. 2018 Jan 31;25(1):8. doi: 10.1186/s12929-018-0409-5.
BACKGROUND
Intake of ethanol (alcohol) has been shown to influence cardiovascular function; the underlying brain mechanism remains unclear. Noting that nitric oxide (NO) system in the CNS is involved in the regulation of cardiovascular function, the present study examined the role of NO in medulla in ethanol-induced cardiovascular changes.
METHODS
Ethanol was administered by oral gavage at dose of 3.2 g/kg once every day for 8 consecutive days. Changes in blood pressure (BP) and heart rate (HR) in response to ethanol were measured by radiotelemetry method in freely moving female Sprague-Dawley rats. NO modulators were applied by intracerebroventricular (ICV) injection. The protein levels of nitric oxide synthase (NOS) and NO content in rostroventral medulla were measured by Western blot and nitrate/nitrite colorimetric assay kit, respectively.
RESULTS
Ethanol intake had little effects on basal BP and HR following 8 consecutive day treatments. A significant increase in HR but not BP following ethanol intake was observed at 6th and 8th, but not at 1st and 4th day treatments as compared with saline group. A decrease in the protein expression of neuronal NOS (nNOS) but not inducible NOS or endothelial NOS and a decline in the level of NO in the medulla 30 min after ethanol administration was observed at 8th day treatment. ICV treatment with NO donors attenuated ethanol-induced tachycardia effects at 8th day treatment. Ethanol produced significantly tachycardia responses when ICV nNOS inhibitors were given at 1st day treatment.
CONCLUSION
Our results suggest that medulla nNOS/NO pathways play an important role in ethanol regulation of HR.
背景
已证实摄入乙醇（酒精）会影响心血管功能；但其潜在的大脑机制尚不清楚。鉴于中枢神经系统中的一氧化氮（NO）系统参与了心血管功能的调节，本研究检测了延髓中 NO 系统在乙醇诱导的心血管变化中的作用。
方法
通过口服灌胃给予 3.2 g/kg 的乙醇，每天一次，连续 8 天。通过无线电遥测法在自由活动的雌性 Sprague-Dawley 大鼠中测量血压（BP）和心率（HR）对乙醇的反应变化。通过脑室内（ICV）注射给予 NO 调节剂。通过 Western blot 和硝酸盐/亚硝酸盐比色测定试剂盒分别测量延髓头端腹外侧区的一氧化氮合酶（NOS）蛋白水平和 NO 含量。
结果
连续 8 天的乙醇摄入后，基础 BP 和 HR 几乎没有受到影响。与生理盐水组相比，在第 6 天和第 8 天的处理中，观察到 HR 显著增加，但 BP 没有增加，而在第 1 天和第 4 天的处理中没有观察到这种增加。与生理盐水组相比，在第 8 天的处理中，观察到神经元型 NOS（nNOS）蛋白表达减少（但诱导型 NOS 或内皮型 NOS 蛋白表达没有减少），以及 30 分钟后 NO 水平下降。在第 8 天的处理中，给予脑室内 NO 供体可减弱乙醇引起的心动过速效应。在第 1 天的处理中给予 nNOS 抑制剂时，乙醇产生了显著的心动过速反应。
结论
我们的结果表明，延髓 nNOS/NO 通路在乙醇对 HR 的调节中起着重要作用。
Zotero 插件