REFLEX CONTROL OF COMPENSATORY RENAL GROWTH & FUNCTION

肾脏参与综合容量调节和循环 通过提供关于其电流的传入神经体液输入来控制 功能水平，并通过调整钠排泄率， 对它们接收到的各种效应器信号的响应。 虽然大部分 存在定义肾脏的这种传出作用的信息， 其他证据表明，存在额外的，不准确的， 描述了神经体液机制，可以参与体积 通过调节Na+来维持体内平衡。 我们实验室的实验 指出，其中一个以前未确定的机制涉及 分泌与γ相同或密切相关的肽， 促黑素细胞激素（gamma-MSH）。 的血浆浓度 免疫反应性（IR）γ-MSH增加与尿钠排泄相关 这是急性单侧肾切除术的结果，而肽本身具有 直接作用于肾脏以增加UNaV。 γ-MSH释放的触发器 包括激活颈动脉窦压力感受器，其提供输入， 中枢神经系统;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 与低盐饮食的大鼠相比，摄入高盐饮食的大鼠也更高 摄入，表明肽的生理调节。 的项目 本申请中所描述的将详细地表征这些因素 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IR- γ-MSH活性;（2）表征颈动脉与 窦和肾传入神经对γ-MSH分泌的调节;（3） 确定负责γ-MSH分泌的垂体叶和 体外释放的调节因子;（4）定量垂体 前体蛋白前阿黑皮素（POMC）信使RNA的含量 在大鼠中摄入钠含量高或低的饮食，并将其与 同时测定血浆和垂体γ-MSH含量;（5）测定 急性期前后γ-MSH代谢清除率 单侧肾切除术 总的来说，这些研究应该大大扩展 我们对这种肽的生物学的理解及其在 容量稳态和循环控制。

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.