GAMMA MSH AND THE PARS INTERMEDIA IN HYPERTENSION

高血压中的 GAMMA MSH 和 PARS 中间体

• 批准号: 3345455
• 负责人: KENNETH A GRUBER
• 金额: $ 9.39万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-30 至 1988-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3345455
• 关键词: adrenocorticotropic hormone; antibody; blood pressure; dopamine; experimental brain lesion; hormone regulation /control mechanism; hypertension; kidney function; kidney metabolism; melanocyte stimulating hormone; radioimmunoassay; sodium; urinalysis

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.

我们已经证明，γ（Gamma）MSH肽具有剂量依赖性， 利尿钠和高血压活性。 流通的主要来源 中间部γ MSH与钠代谢有关。 此外，抑制中间部分泌的多巴胺激动剂， 具有降压作用。 这些数据表明， 中间部，特别是γ MSH，在肾脏和心血管 physiology. 本研究旨在探讨γ-MSH的作用机制， 诱导高血压，并开始辨别伽马MSH的作用， 中间部在容量和心血管调节中的作用。 将通过使用慢性动脉内 或脑室内输注。 这将使我们能够 比较中枢效应和外周效应。 的可能机制 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 血管收缩剂和肾上腺皮质激素的分泌。 伽马MSH和中间部的生理作用将是 在盐水扩张和DOC-盐高血压大鼠中检查。 这些 实验将包括：测量循环γ MSH，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和注射 伽马MSH抗体 我们将把这些测量结果关联起来， 对血压和钠排泄的干预。 快速推注和输注γ-MSH对肾脏的影响 将通过测量肾血流量，肾小球滤过率， 和钠排泄分数。 交感神经系统贡献 将由肾上腺素能的选择性药理学阻断决定 受体和使用去神经支配的肾脏。 这项建议的成功实施将有助于确定一个 以前未被认识到的肾和心血管系统调节类 激素，并提供了哺乳动物中间部的可能作用， physiology.