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GAMMA MSH AND THE CARDIOVASCULAR RESPONSE TO STRESS

GAMMA MSH 和心血管对压力的反应

基本信息

批准号：
3348700
负责人：
KENNETH A GRUBER
金额：
$ 8.88万
依托单位：
WAKE FOREST UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-30 至 1989-09-29
项目状态：
已结题

项目摘要

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.

垂体前阿黑皮素（POMC）肽分泌增加，在许多形式的压力中被发现。我们最近报道说，相对较新的一类POMC肽，γ MSH具有独特的心血管活动，包括交感神经系统激活和副交感神经系统抑制。我们建议研究伽马MSH肽在心血管效应中的作用，一个不可避免的轻音电击模式。监测的心血管参数将是动脉压、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. Gamma MSH增强应激诱导的心血管变化输注：ii.减轻压力引起的心血管效应，神经中间叶切除术（NLx）（消除主要外周POMC）系统），以及在其他大鼠中，将NLx与弓状核病变相结合（消除CNS伽马MSH系统的主要部分）（以证明这些病变的影响是由于减少伽马MSH肽，我们将尝试用伽马MSH恢复缺陷输注）; iii.循环POMC肽的放射免疫测定，包括伽马MSH，试图评估在压力下的中叶活动，将其与我们的心血管参数中的一个或多个相关联;以及iv. 间歇性应激对心血管的影响用生理盐水进行体积扩张。有证据表明，不平衡增加中叶激素的分泌。的已经假定存在垂体利钠激素，从未被确认。我们发现γ MSH肽具有利尿钠作用在剂量显著低于产生心血管方面的影响. 盐膨胀对应激诱导MAP的增强作用升高可归因于单个升压器的共同激活系统外周的，也可能是中枢的，γ-MSH 肽可能是这个因素将通过使用NLx进行研究，以阻止压力下盐水膨胀的升压作用。我们还将测量循环POMC肽（包括γ MSH），当压力和体积扩张相结合，以显示增强的中叶分泌物这些实验旨在探索一类新的POMC衍生肽的心血管活性可以在自主神经系统对压力的反应中起着重要作用。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

ACTH-(4-10) through gamma-MSH: evidence for a new class of central autonomic nervous system-regulating peptides.

ACTH-(4-10) 至 γ-MSH：一类新型中枢自主神经系统调节肽的证据。

DOI：
10.1152/ajpregu.1989.257.4.r681
发表时间：
1989
期刊：
The American journal of physiology
影响因子：
0
作者：
Gruber,KA;Callahan,MF
通讯作者：
Callahan,MF

ACTH-induced hypertension in rats: fact or artifact?

ACTH 诱发的大鼠高血压：事实还是人为因素？

DOI：
10.1152/ajpregu.1989.256.6.r1308
发表时间：
1989
期刊：
The American journal of physiology
影响因子：
0
作者：
Gruber,KA;Eskridge-Sloop,SL;Eldridge,JC;Callahan,MF
通讯作者：
Callahan,MF

Central oxytocin systems may mediate a cardiovascular response to acute stress in rats.

中枢催产素系统可能介导大鼠对急性应激的心血管反应。

DOI：
10.1152/ajpheart.1989.256.5.h1369
发表时间：
1989
期刊：
The American journal of physiology
影响因子：
0
作者：
Callahan,MF;Kirby,RF;Cunningham,JT;Eskridge-Sloop,SL;Johnson,AK;McCarty,R;Gruber,KA
通讯作者：
Gruber,KA

Central administration of angiotensin II receptor antagonists and arterial pressure regulation: a note of caution.

血管紧张素 II 受体拮抗剂的中枢给药和动脉压调节：注意事项。