ORGANIZATION OF CENTRAL SYMPATHETIC PATHWAYS

现在人们认识到，吻侧延髓腹外侧 哺乳动物(RVL)在交感神经的产生中起着重要作用 血管运动流出和维持动脉压。它的重要性 RVL的发生，特别是在麻醉状态下，似乎是由于以下原因 主要原因有三：i)这个核团含有兴奋性神经元 直接投射到脊髓的中间外侧细胞柱 脊髓II)这些细胞中有许多具有内在起搏器 活动和三)相同的细胞也在 各种血管舒缩反射。其中许多自体细胞是 非儿茶酚胺能，但球脊髓肾上腺素能 RVL的细胞(C1细胞)也参与交感神经张力的产生 有极具提示性的证据支持。还有一些 表明G1细胞可能是常用的 交感神经药物可乐定和这些细胞的过度活动 可能在遗传性高血压中起作用。 这些概念对于理解大脑是如何 调节血液流动，需要额外的和 希望是确凿的证据。因此，目前的目标是 建议完全描述RVL G1细胞的解剖学特征， 生理学和药理学观点，并确定其 在遗传性高血压中的作用。需要检验的关键假设是：a) 肾上腺素能和谷氨酸能细胞代表两个不同的群体 交感前运动神经元，b)两者都具有自律性和 向血管运动性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复发性侧支相互作用 由α2-肾上腺素能受体介导，d)这些抑制性受体 是中枢抗交感神经和降压药物的主要靶点 可乐定与c1肾上腺素能细胞的异常高活性 导致遗传性交感神经外流增加 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.