ORGANIZATION OF CENTRAL SYMPATHETIC PATHWAYS

现在已经认识到延髓腹外侧头端 (RVL)在产生交感神经系统中起着至关重要的作用。 血管流出和维持动脉压。的重要性 RVL，特别是在麻醉下，似乎是由于以下原因 三个主要原因：i）该核含有兴奋性神经元， 直接投射到脊髓的中间外侧细胞柱 脊髓ii）这些细胞中的许多被赋予了内在的起搏点 活性和iii）相同的细胞也发挥关键的整合作用， 各种血管反射许多这些自激活细胞 但球脊髓肾上腺素能神经 RVL细胞（C1细胞）也参与交感神经紧张的产生 都有非常有启发性的证据支持也有一些 这表明G1细胞可能是常用的 交感神经阻滞药可乐定和这些细胞的过度活跃 可能在遗传性高血压中起作用。 这些概念对于理解大脑如何 调节血液流动，需要额外的支持， 希望能找到确凿的证据因此，本发明的目标 建议是从解剖学上完全表征RVLG 1细胞， 生理和药理学观点，并确定其 在遗传性高血压中的作用。待检验的关键假设为：a） 肾上腺素能和肾上腺素能细胞代表两个独立的群体 交感神经前运动神经元，B）两者都具有自激活特性， 对血管神经节前神经元贡献兴奋性驱动，c） 肾上腺素能细胞具有抑制性的循环侧支相互作用 由α 2-肾上腺素能受体介导，d）这些抑制性受体 是中枢交感神经阻滞剂和镇静剂的主要目标 可乐定和e）C1肾上腺素能细胞的异常高活性 有助于增加交感神经流出的遗传 高血压

It is now recognized that the rostral ventrolateral medulla oblongata (RVL) of mammals plays an essential role in generating the sympathetic vasomotor outflow and in maintaining arterial pressure. The importance of RVL, especially under anesthesia, seems to be due to the following three main reasons: i) this nucleus contains excitatory neurons which project directly to the intermediolateral cell column of the spinal cord ii) many of these cells are endowed with intrinsic pacemaker activity and iii) the same cells also play a key integrative role in a variety of vasomotor reflexes. Many of these autoactive cells are non-catecholaminergic but the notion that the bulbospinal adrenergic cells of RVL (C1 cells) also participate in sympathetic tone generation is backed by extremely suggestive evidence. There is also some indication that G1 cells could be a target of the commonly used sympatholytic drug clonidine and that the hyperactivity of these cells could play a role in genetic hypertension. These concepts are central to an understanding of how the brain regulates blood flow and they need to be supported by additional and hopefully definitive evidence. Accordingly, the goal of the present proposal is to fully characterize RVL G1 cells from an anatomical, physiological and pharmacological standpoint and to determine their role in genetic hypertension. The key hypotheses to be tested are: a) adrenergic and glutamatergic cells represent two separate populations of sympathetic premotorneurons, b) both have autoactive properties and contribute an excitatory drive to vasomotor preganglionic neurons, c) adrenergic cells have inhibitory recurrent collateral interactions mediated by alpha2-adrenergic receptors, d) these inhibitory receptors are a major target of the central sympatholytic and hypotensive drug clonidine and e) the abnormally high activity of C1 adrenergic cells contributes to the increased sympathetic outflow in genetic hypertension.