ENDOGENOUS OPIATE PEPTIDES AND CARDIOVASCULAR CONTROL

交感神经系统在心脏控制中的重要性 血管已经建立。 最近，一个强大的系统， 交感神经释放去甲肾上腺素（NE）的肽能调节， 被描述。 Met-和Leu-脑啡肽突触前抑制 NE来自交感神经末梢。 这些肽已被证明是 肾上腺髓质嗜铬细胞和其他细胞中与NE和肾上腺素共存 节后交感神经细胞 它们与 通过各种刺激的儿茶酚胺。 因此，一种机制的存在 用于在神经水平调节NE的交感神经释放 终点站已经建立。 然而，这一机制在任何 完整生物体的生理或病理生理状态 确立了习 尽管这种机制可以在各种不同的环境中起作用， 在紧张的情况下，我们建议最初将调查重点放在 其在清醒时低血压伴出血中的作用 兔子 我们发现交感神经活动的反常减少 在从正常到低血压过渡的出血期间。 我们的飞行员 实验强烈提示肾上腺髓质脑啡肽可能是 负责这一下降。 我们的假设是 肾上腺髓质释放的甲硫氨酸脑啡肽抑制交感神经 NE的释放并导致转变为低血压。 我们将测试 以下具体假设：1）血浆脑啡肽水平在 出血和上升的时间过程与过渡相关 肾上腺髓质是脑啡肽的来源 脑啡肽交感神经抑制 通过突触前抑制机制诱导外周血管收缩; 和4）纳洛酮逆转与低血压相关的 出血是由于外周而不是中枢阿片的拮抗作用 受体。 这些研究将使用长期仪器进行， 清醒的兔子 血浆和肾上腺组织甲硫氨酸脑啡肽将 使用放射免疫测定法测量。 血浆和肾上腺儿茶酚胺将 通过高压液相色谱法和电化学 侦测 这项拟议中的研究是记录 假设该脑啡肽能系统在调节中具有强大的作用 交感神经活动，因此，在心血管控制在完整的 有机体

The importance of the sympathetic nervous system in control of heart and blood vessels is well established. Recently a potent system that involves peptidergic modulation of sympathetic release of norepinephrine (NE) has been described. Met- and leu-enkephalin presynaptically inhibit release of NE from sympathetic nerve terminals. These peptides have been shown to be costored with NE and epinephrine in adrenal medullary chromaffin and other postganglionic sympathetic cells. They are coreleased with the catecholamines by a variety of stimuli. Thus, the eixstence of a mechanism for modulation of sympathetic release of NE at the level of the nerve terminal is firmly established. However, the role of this mechanism in any physiological or pathophysiological state in the intact organism has not been established. Although this mechanism may function in a variety of stressful situations, we propose to initially focus our investigation on its role in the hypotension associated with hemorrhage in the conscious rabbit. We have identified a paradoxical decrease in sympathetic activity during hemorrhage at the transition from normo- to hypotension. Our pilot experiments strongly suggest that adrenal medullary enkephalins may be responsible for this decrease. Our general hypothesis is that met-enkephalin released by the adrenal medulla depresses sympathetic release of NE and causes the transition to hypotension. We will test the following specific hypotheses: 1) plasma enkephalin levels rise during hemorrhage and the time course of the rise correlates with the transition to hypotension; 2) the adrenal medulla is the source of the enkephalins that produce the CV depression; 3) the enkephalins inhibit sympathetically induced peripheral vasoconstriction by a presynaptic inhibitory mechanism; and 4) the reversal by naloxone of the hypotension associated with hemorrhage is due to antagonism of peripheral rather than central opiate receptors. These studies will be performed using chronically instrumented conscious rabbits. Plasma and adrenal tissue met-enkephalin will be measured using radioimmunoassay. Plasma and adrenal catecholamines will be measured by high pressure liquid chromatography with electrochemical detection. The proposed study is an important first step in documenting the hypothetically potent role of this enkephalinergic system in modulation of sympathetic activity and thus, in cardiovascular control in the intact organism.