Role of the Sympathetic Nervous System in Schlager Genetically Hypertensive Mice
Role of the Sympathetic Nervous System in Schlager Genetically Hypertensive Mice
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DOI：
10.1161/hypertensionaha.109.136069
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发表时间：
2009-10-01
期刊：
影响因子：
8.3
通讯作者：
Head, Geoffrey A.
中科院分区：
文献类型：
--
作者：
Davern, Pamela J.;Nguyen-Huu, Thu-Phuc;Head, Geoffrey A.
早期的研究表明，在Schlager近交系小鼠身上观察到的高血压可能归因于一种神经性机制。在这项研究中，我们研究了交感神经系统在维持BPH/2J小鼠高血压中的作用，并使用c-Fos免疫组织化学方法来阐明特定脑区的神经元激活是否与清醒血压有关。在雄性高血压(BPH/2J；n=14)、正常血压(BPN/3J；n=18)和C57/BL6(n=5)小鼠体内植入遥测装置，在恢复10天后记录血压、心率和运动活动，以确定昼夜节律变化。BPH/2J小鼠的平均动脉压高于BPN/3J或C57/BL6小鼠(P<；0.001)，且BPH/2J小鼠的昼夜差异被夸大(BPN/3J小鼠为17+/-2 mm Hg或C57/BL6小鼠为+8+/-2 mm Hg；P<；0.001)。在BPH/2J和BPN/3J小鼠的活动期和非活动期，急性交感神经阻断(7.5 mg/kg ip)可使BPH/2J和BPN/3J小鼠的血压降低到类似的水平。与BPn/3J小鼠相比，高血压活动期BPH/2J小鼠杏仁核(+180%)、室旁核(+110%；P<；0.001)和下丘脑背内侧(+48%；P<；0.001)的c-Fos标记细胞数量较多。在非活动期，这些区域的神经元激活水平基本相似。在所有被研究的区域中，c-Fos检测到杏仁内侧核神经元的激活与平均动脉压高度相关(r=0.98)。这些发现表明，高血压在很大程度上可归因于交感神经系统的活动，可能是由杏仁内侧核神经元调节的更高水平的唤醒产生的。(高血压。2009年；54：852-859。)
Early studies indicate that the hypertension observed in the Schlager inbred mouse strain may be attributed to a neurogenic mechanism. In this study, we examined the contribution of the sympathetic nervous system in maintaining hypertension in the BPH/2J mouse and used c-Fos immunohistochemistry to elucidate whether neuronal activation in specific brain regions was associated with waking blood pressure. Male hypertensive (BPH/2J; n = 14), normotensive (BPN/3J; n = 18), and C57/Bl6 (n = 5) mice were implanted with telemetry devices, and after 10 days of recovery, recordings of blood pressure, heart rate, and locomotor activity were measured to determine circadian variation. Mean arterial pressure was higher in BPH/2J than in BPN/3J or C57/Bl6 mice (P < 0.001), and BPH/2J animals showed exaggerated day-night differences (17 +/- 2 versus 6 +/- 1 mm Hg in BPN/3J or +8 +/- 2 mm Hg in C57/Bl6 mice; P < 0.001). Acute sympathetic blockade with pentolinium (7.5 mg/kg IP) during the active and inactive phases reduced blood pressure to comparable levels in BPH/2J and BPN/3J mice. The number of c-Fos-labeled cells was greater in the amygdala (+180%; P < 0.01), paraventricular nucleus (+110%; P < 0.001), and dorsomedial hypothalamus (+48%; P < 0.001) in the active (hypertensive) phase in BPH/2J compared with BPN/3J mice. The level of neuronal activation was mostly similar in these regions in the inactive phase. Of all of the regions studied, neuronal activation in the medial amygdala, as detected by c-Fos, was highly correlated to mean arterial pressure (r = 0.98). These findings indicate that the hypertension is largely attributable to sympathetic nervous system activity, possibly generated through greater levels of arousal regulated by neurons located in the medial amygdala. (Hypertension. 2009; 54: 852-859.)