ORGANIZATION OF CENTRAL SYMPATHETIC PATHWAYS

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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.