Department of Physiology, University of Melbourne, Parkville, VIC 3010, Australia.
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
Cell Metab. 2017 Mar 7;25(3):739-748. doi: 10.1016/j.cmet.2017.01.019. Epub 2017 Feb 16.
The etiology of hypertension, the world's biggest killer, remains poorly understood, with treatments targeting the established symptom, not the cause. The development of hypertension involves increased sympathetic nerve activity that, in experimental hypertension, may be driven by excessive respiratory modulation. Using selective viral and cell lesion techniques, we identify adrenergic C1 neurons in the medulla oblongata as critical for respiratory-sympathetic entrainment and the development of experimental hypertension. We also show that a cohort of young, normotensive humans, selected for an exaggerated blood pressure response to exercise and thus increased hypertension risk, has enhanced respiratory-related blood pressure fluctuations. These studies pinpoint a specific neuronal target for ameliorating excessive sympathetic activity during the developmental phase of hypertension and identify a group of pre-hypertensive subjects that would benefit from targeting these cells.
高血压是世界上最大的杀手之一,但病因仍不清楚,目前的治疗方法针对的是已确立的症状,而不是病因。高血压的发展涉及到交感神经活动的增加,在实验性高血压中,这种增加可能是由过度的呼吸调节驱动的。使用选择性病毒和细胞损伤技术,我们确定延髓中的肾上腺素能 C1 神经元对于呼吸-交感神经的同步化和实验性高血压的发展至关重要。我们还表明,一组年轻的、血压正常的人,由于对运动的血压反应过度而选择,因此高血压风险增加,他们的血压波动与呼吸相关。这些研究确定了一个特定的神经元靶点,以在高血压的发展阶段改善过度的交感神经活动,并确定了一组可能受益于靶向这些细胞的高血压前期患者。