GAMMA MSH AND THE PARS INTERMEDIA IN HYPERTENSION

我们已经证明了伽马(Gamma)MSH多肽具有剂量依赖性 利钠和高血压活性。流通的主要来源 中间部的伽玛-MSH被认为与钠代谢有关。 此外，抑制中间部分分泌的多巴胺激动剂， 有降压作用。这些数据表明， 肾脏和心血管的中间部，特别是伽玛-MSH 生理学。这项建议是为了研究伽玛MSH的机制， 诱发性高血压，并开始认识伽玛MSH和 间隔部的容量和心血管调节。 伽玛-MSH高血压将通过慢性动脉内注射进行研究 或大鼠脑室内输液。这将使我们能够 比较中枢效应与外周效应。可能的机制 研究包括：交感神经系统激活，直接 血管效应、压力感受器重置、内源性增强 血管收缩药和肾上腺皮质激素的分泌。 伽玛MSH和中间部分的生理作用将是 在生理盐水扩张和DOC盐高血压大鼠身上进行了检测。这些 实验将包括：循环伽玛MSH的测量，抑制 地塞米松和/或溴隐亭对垂体γ-MSH分泌的影响 治疗，选择性切除神经中间叶，注射 伽玛MSH抗体。我们将关联这些测量结果或 对血压和钠排泄的干预。 γ-MSH团注与静脉滴注对肾脏的影响 将通过测量肾脏血流量，肾小球滤过率， 和部分钠的排泄。交感神经系统贡献 将通过选择性药物阻断肾上腺素能来确定 受体和失神经肾脏的使用。 这项提议的成功实施可能有助于界定 以前未被认识的肾脏和心血管系统调节类别 激素，并为哺乳动物的中间部提供了可能的作用 生理学。

We have demonstrated that gamma (Gamma) MSH peptides have dose-dependent natriuretic and hypertensive activity. The major source of circulating Gamma MSH, the pars intermedia, has been implicated in sodium metabolism. In addition, dopamine agonists, which inhibit pars intermedia secretion, have antihypertensive effects. These data suggest a possible role for the pars intermedia, specifically Gamma MSH, in renal and cardiovascular physiology. This proposal is to investigate the mechanism of Gamma MSH, induced hypertension, and to begin to discern the role of Gamma MSH and the pars intermedia in volume and cardiovascular regulation. Gamma MSH hypertension will be investigated by using chronic intra-arterial or intracerebroventricular infusions in rats. This will allow us to compare central vs. peripheral effects. Possible mechanisms for investigation include; sympathetic nervous system activation, direct vascular effects, resetting of baroreceptors, potentiation of endogenous vasoconstrictors, and secretion of adrenocorticoids. The physiological role of Gamma MSH and the pars intermedia will be examined in saline-expanded and DOC-salt hypertensive rats. These experiments will include; measurement of circulating Gamma MSH, inhibition of hypophyseal Gamma MSH secretion by dexamethasone and/or bromocryptine treatment, selective removal of the neurointermediate lobe, and injection of Gamma MSH antibodies. We will correlate these measurements or interventions to blood pressure and sodium excretion. The renal effects of bolus injections and infusions of Gamma MSH in rate will be examined by measuring renal blood flow, glomerular filtration rate, and fractional sodium excretion. Sympathetic nervous system contributions will be determined by selective pharmacological blockage of adrenergic receptors and the use of denervated kidneys. The successful implementation of this proposal could help define a previously unrecognized class of renal and cardiovascular system regulating hormones, and provide a possible role for the pars intermedia in mammalian physiology.