GAMMA MSH AND THE CARDIOVASCULAR RESPONSE TO STRESS

GAMMA MSH 和心血管对压力的反应

• 批准号: 3348699
• 负责人: KENNETH A GRUBER
• 金额: $ 8.11万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3348699
• 关键词: autonomic nervous system; baroreceptors; behavioral medicine; cardiovascular function; cardiovascular pharmacology; experimental brain lesion; heart innervation; heart rate; hormone regulation /control mechanism; hypertension; hypophysectomy; hypothalamic pituitary axis; kidney; median eminence; melanocyte stimulating hormone; radioimmunoassay; saluresis; secretion; stress; ultrasound blood flow measurement; vascular resistance; vasoactive agent

Increased secretion of pituitary pro-opiomelanocortin (POMC) peptides has been found in many forms of stress. We have recently reported that a relatively new class of POMC peptides, the gamma MSH's have unique cardiovascular activities, which include sympathetic nervous system activation and parasympathetic nervous system inhibition. We propose to investigate the role of Gamma MSH peptides in the cardiovascular effects of an unavoidable light-tone-footshock paradigm. The monitored cardiovascular parameters will be arterial pressure, heart rate, regional vascular resistance, and baroreceptor function. Our experiments will include: i. potentiation of stress-induced cardiovascular alterations by Gamma MSH infusions: ii. blunting to stress-induced cardiovascular effects by neurointermediate lobectomy (NLx) (elimination of a major peripheral POMC system), and in other rats, combining NLx with arcuate nucleus lesions (elimination of a major part of the CNS Gamma MSH system) (to demonstrate that the effects of these lesions are specifically due to reductions in Gamma MSH peptides, we will attempt to restore the deficits with Gamma MSH infusions); iii. radioimmunoassay of circulating POMC peptides, including Gamma MSH, in an attempt to assess intermediate lobe activity in stress and correlate it to one or more of our cardiovascular parameters; and iv. potentiation of the cardiovascular effects of stress by intermittent volume-expansion with saline. There is evidence that states of hydrominral inbalance increase the secretion of intermediate lobe hormones. The existence of a hypophyseal natriuretic hormone has been postulated but never identified. We have found the Gamma MSH peptides have natriuretic activity at doses significantly below those which produce cardiovascular effects. The potentiation by saline-expansion of a stress-induced MAP elevation could be attributed to common activation of a single pressor system. The possibility that peripheral, and possibly central, Gamma MSH peptides may be this factor will be investigated by using NLx in an attempt to block the pressor effects of saline expansion in stress. We will also measure circulating POMC peptides (including Gamma MSH) when stress and volume expansion are combined to demonstrate enhanced intermediate lobe secretion. These experiments are designed to explore the possibility that the cardiovascular activities of a new class of POMC derived peptides may play an important role in the autonomic nervous system response to stress.

垂体促阿片黑素皮质素原(POMC)多肽分泌增加 存在于多种形式的压力中。我们最近报道了一个 相对较新的一类POMC多肽，伽马MSH具有独特的 心血管活动，包括交感神经系统 激活和抑制副交感神经系统。我们建议 探讨γ-MSH多肽在高血压大鼠心血管效应中的作用 一个不可避免的轻声脚步震撼范例。被监测的心血管疾病 参数包括动脉压、心率、局部血管 阻力和压力感受器功能。我们的实验将包括：i. γ-MSH对应激诱导的心血管改变的增强作用 输液：II。钝化应激诱导的心血管效应 神经中间叶切除术(NLX)(消除主要外周POMC 在其他大鼠中，NLX与弓状核损毁相结合 (取消CNS伽玛MSH系统的主要部分)(演示 这些损伤的影响特别是由于减少了 伽马MSH多肽，我们将尝试用伽马MSH恢复赤字 输液)；iii.循环POMC多肽的放射免疫分析，包括 Gamma MSH，以试图评估应激和 将其与我们的一个或多个心血管参数相关联；以及 间歇性应激对心血管的影响 用生理盐水扩容。有证据表明，水合作用状态 失衡增加中间叶激素的分泌。这个 已经假设存在一种脑垂体利钠激素，但 从未被确认身份。我们发现伽玛MSH多肽具有利钠作用 显著低于产生心血管疾病的剂量的活动 效果。盐胀对应激性MAP的增强作用 升高可以归因于单一加压的共同激活 系统。外周，也可能是中枢伽玛MSH 多肽可能是这一因素将通过使用NLX进行研究的一种尝试 在应激状态下阻断生理盐水扩张的升压作用。我们还将 应激时测定循环POMC肽(包括γ-MSH) 结合体积扩张显示强化的中间叶 分泌物。这些实验旨在探索一种可能性 一类新的POMC衍生肽的心血管活性可能 在自主神经系统对压力的反应中起着重要作用。