Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.
Hypertension. 2013 Jul;62(1):118-25. doi: 10.1161/HYPERTENSIONAHA.113.01404. Epub 2013 May 13.
Proinflammatory cytokines play an important role in regulating autonomic and cardiovascular function in hypertension and heart failure. Peripherally administered proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), act on the brain to increase blood pressure, heart rate, and sympathetic nerve activity. These molecules are too large to penetrate the blood-brain barrier, and so the mechanisms by which they elicit these responses remain unknown. We tested the hypothesis that the subfornical organ (SFO), a forebrain circumventricular organ that lacks a blood-brain barrier, plays a major role in mediating the sympathetic and hemodynamic responses to circulating proinflammatory cytokines. Intracarotid artery injection of TNF-α (200 ng) or IL-1β (200 ng) dramatically increased mean blood pressure, heart rate, and renal sympathetic nerve activity in rats with sham lesions of the SFO (SFO-s). These excitatory responses to intracarotid artery TNF-α and IL-1β were significantly attenuated in SFO-lesioned (SFO-x) rats. Similarly, the increases in mean blood pressure, heart rate, and renal sympathetic nerve activity in response to intravenous injections of TNF-α (500 ng) or IL-1β (500 ng) in SFO-s rats were significantly reduced in the SFO-x rats. Immunofluorescent staining revealed a dense distribution of the p55 TNF-α receptor and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, in the SFO. These data suggest that SFO is a predominant site in the brain at which circulating proinflammatory cytokines act to elicit cardiovascular and sympathetic responses.
促炎细胞因子在高血压和心力衰竭中调节自主神经和心血管功能方面发挥着重要作用。外周给予促炎细胞因子，如肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β），会作用于大脑，增加血压、心率和交感神经活动。这些分子太大，无法穿透血脑屏障，因此它们引发这些反应的机制尚不清楚。我们检验了这样一个假设，即侧脑室下器官（SFO）作为一个缺乏血脑屏障的前脑室周器官，在介导循环促炎细胞因子引起的交感神经和血液动力学反应中发挥主要作用。在 SFO 假损伤（SFO-s）大鼠中，经颈动脉内注射 TNF-α（200ng）或 IL-1β（200ng）可显著增加平均血压、心率和肾交感神经活动。SFO 损伤（SFO-x）大鼠中，对颈动脉内 TNF-α和 IL-1β的这些兴奋反应明显减弱。同样，在 SFO-s 大鼠中，静脉内注射 TNF-α（500ng）或 IL-1β（500ng）引起的平均血压、心率和肾交感神经活动的增加，在 SFO-x 大鼠中也明显减少。免疫荧光染色显示，在 SFO 中存在密集分布的 p55 TNF-α受体和白细胞介素-1受体辅助蛋白，即白细胞介素-1 受体的一个亚基。这些数据表明，SFO 是大脑中一个主要的部位，循环促炎细胞因子在此作用于大脑，引发心血管和交感神经反应。
