ENDOGENOUS OPIATE PEPTIDES AND CARDIOVASCULAR CONTROL

交感神经系统在控制心脏和心脏功能中的重要性 血管长得很好。最近，一个强大的系统涉及到 去甲肾上腺素(NE)交感神经释放的肽能调制 都被描述过。甲硫氨酸和亮氨酸脑啡肽抑制突触前神经递质释放 来自交感神经末梢的神经。这些多肽已经被证明是 肾上腺髓质嗜铬细胞等与去甲肾上腺素和肾上腺素共沉积 节后交感细胞。它们与 儿茶酚胺通过各种刺激。因此，一种机制的存在 在神经水平上调制去甲肾上腺素的交感神经释放 终端已经牢牢建立起来了。然而，这一机制在任何 完整生物体的生理或病理生理状态没有 已经建立了。尽管这种机制可以在各种 有压力的情况下，我们建议将最初的调查重点放在 它在意识出血相关低血压中的作用 兔子。我们发现交感神经活动出现了矛盾的下降。 在从正常血压到低血压的转变过程中出血。我们的飞行员 实验有力地表明，肾上腺髓质脑啡肽可能是 造成这一下降的原因。我们的一般假设是 肾上腺髓质释放甲硫氨酸脑啡肽抑制交感神经 去甲肾上腺素的释放导致向低血压的过渡。我们将测试 以下具体假设：1)血浆脑啡肽水平在 出血和上升的时间进程与转变相关 2)肾上腺髓质是脑啡肽的来源。 3)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； 4)纳洛酮逆转与高血压相关的低血压 出血是由于外周的拮抗作用，而不是中枢阿片类药物。 感受器。这些研究将使用慢性仪器进行 清醒的兔子。血浆和肾上腺组织甲硫氨酸脑啡肽 用放射免疫测定法测定。血浆和肾上腺儿茶酚胺将是 高压液相色谱-电化学法测定 侦测。拟议的研究是记录文件的重要第一步 假设这个脑啡肽能系统在调制中起着强有力的作用 交感神经活动，因此，在完整的心血管控制中 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.