REFLEX CONTROL OF COMPENSATORY RENAL GROWTH AND FUNCTION

肾脏参与整体容量调节和循环 通过提供关于其电流的传入神经体液输入进行控制 功能水平，并通过调整体内钠的排泄率 对它们接收到的各种效应器信号作出反应。虽然很多 有信息可以定义肾脏的这种传出作用，多个 其他证据表明，不准确地说，存在额外的 描述了参与卷的神经体液机制 通过调节Na来实现动态平衡。我们实验室的实验已经 表示其中一种以前未确定的机制涉及 分泌一种与γ-相同或密切相关的多肽 黑素细胞刺激素(γ-MSH)。血药浓度 与钠尿相关的免疫反应性(IR)γ-MSH增加 这是由急性单侧肾切除引起的，而这种多肽本身就有 增加UNaV的直接肾脏作用。伽马-MSH释放的触发因素 包括激活颈动脉窦压力感受器，它为 中枢神经系统；多肽的分泌也依赖于 来自肾传入神经的输入。血浆IR-γ-MSH浓度为 摄入高盐饮食的大鼠也高于低盐饮食的大鼠 摄取，暗示了多肽的生理调节。这些项目 在本申请中描述的将详细描述这些因素 通过(1)调节γ-MSH样肽的分泌和代谢 确定刺激肾传入神经是否增加血浆胰岛素抵抗。 伽玛-MSH活性；(2)表征颈动脉之间的相互作用 窦、肾传入神经对γ-MSH分泌的调节作用； 确定负责分泌γ-MSH的脑垂体叶和 调节其体外释放的因子(S)；(4)脑垂体定量 前体蛋白前阿片黑素皮质素信使RNA的含量 在摄入高或低钠含量的饮食的大鼠中，这与 同时测定血浆和脑垂体中γ-MSH的含量 急性加重期前后γ-MSH的代谢清除率 单侧肾切除术。总体而言，这些研究应该大大扩展 我们对这种多肽的生物学特性及其在 体量平衡和循环控制。

The kidneys participate in integrated volume regulation and circulatory control by providing afferent neurohumoral input regarding their current level of functioning, and by adjusting the rate of sodium excretion in response to the various effector signals which they receive. Although much information exists to define this efferent role of the kidneys, multiple other lines of evidence indicate the existence of additional, imprecisely described neurohumoral mechanisms that could participate in volume homeostasis by regulating Na. Experiments from our laboratory have indicated that one such previously unidentified mechanism involves the secretion of a peptide identical with or closely related to gamma- melanocyte stimulating hormone (gamma-MSH). The plasma concentration of immunoreactive (IR) gamma-MSH increases in association with the natriuresis that results from acute unilateral nephrectomy, and the peptide itself has a direct renal action to increase UNaV. The trigger for gamma-MSH release includes activation of carotid sinus baroreceptors, which provide input to the central nervous system; secretion of the peptide is also dependent on input from renal afferent nerves. Plasma IR-gamma-MSH concentration is also higher in rats ingesting high salt diet compared to rats on a low salt intake, suggesting physiologic regulation of the peptide. The projects described in this application will characterize in detail the factors regulating the secretion and metabolism of gamma-MSH-like peptides by (1) determining if stimulation of renal afferent nerves increases plasma IR- gamma-MSH activity; (2) characterizing the interaction between carotid sinus and renal afferents in the regulation of gamma-MSH secretion; (3) identifying the pituitary lobe responsible for gamma-MSH secretion and the factor(s) mediating its release in vitro; (4) quantitating the pituitary content of the precursor protein proopiomelanocortin (POMC) messenger RNA in rats ingesting diets high or low in sodium content, and relating this to simultaneous plasma and pituitary contents of gamma-MSH; (5) determining the metabolic clearance rate of gamma-MSH, before and after acute unilateral nephrectomy. These studies should in aggregate extend greatly our understanding of the biology of this peptide and its importance in volume homeostasis and circulatory control.