Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA.
Department of Health and Human Physiology, University of Iowa, Iowa City, IA, USA.
Nat Rev Nephrol. 2018 Dec;14(12):750-766. doi: 10.1038/s41581-018-0068-5.
The causes of essential hypertension remain an enigma. Interactions between genetic and external factors are generally recognized to act as aetiological mechanisms that trigger the pathogenesis of high blood pressure. However, the questions of which genes and factors are involved, and when and where such interactions occur, remain unresolved. Emerging evidence indicates that the hypertensive response to pressor stimuli, like many other physiological and behavioural adaptations, can become sensitized to particular stimuli. Studies in animal models show that, similarly to other response systems controlled by the brain, hypertensive response sensitization (HTRS) is mediated by neuroplasticity. The brain circuitry involved in HTRS controls the sympathetic nervous system. This Review outlines evidence supporting the phenomenon of HTRS and describes the range of physiological and psychosocial stressors that can produce a sensitized hypertensive state. Also discussed are the cellular and molecular changes in the brain neural network controlling sympathetic tone involved in long-term storage of information relating to stressors, which could serve to maintain a sensitized state. Finally, this Review concludes with a discussion of why a sensitized hypertensive response might previously have been beneficial and increased biological fitness under some environmental conditions and why today it has become a health-related liability.
原发性高血压的病因仍然是一个谜。一般认为，遗传和外部因素之间的相互作用是引发高血压发病机制的病因机制。然而，涉及哪些基因和因素，以及这种相互作用何时何地发生，这些问题仍未得到解决。新出现的证据表明，高血压对升压刺激的反应，就像许多其他生理和行为适应一样，可以对特定的刺激变得敏感。动物模型研究表明，与大脑控制的其他反应系统一样，高血压反应敏化（HTRS）是由神经可塑性介导的。参与 HTRS 的大脑回路控制着交感神经系统。本综述概述了支持 HTRS 现象的证据，并描述了一系列可能导致高血压敏感状态的生理和心理社会应激源。本文还讨论了参与控制交感神经张力的大脑神经网络中与应激源相关信息的长期储存有关的细胞和分子变化，这些变化可能有助于维持敏感状态。最后，本综述讨论了为什么在某些环境条件下，高血压的敏感反应以前可能是有益的，并提高了生物适应性，而今天它已成为与健康相关的不利因素。
