BAROREFLEX FUNCTION: MODULATION BY NEUROPEPTIDES

压力反射功能：神经肽的调节

基本信息

批准号：
3449411
负责人：
LAUREL A FISHER
金额：
$ 5.4万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-04-01 至 1987-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3449411
关键词：
baroreceptors central nervous system chemical reaction corticotropin releasing factor heart rate hypertension neurons

项目摘要

The general objective of the proposed research is to examine the roles of two neuropeptides, corticotropin-releasing factor (CRF) and bombesin, in the central nervous system (CNS) regulation of the baroreceptor reflex. Baroreflex control of blood pressure is effected primarily through adjustments of sympathetic (SNS) and parasympathetic (PNS) outflow to the heart and vasculature. Since CRF and bombesin have profound CNS actions to influences SNA and PNS activity, blood pressure and heart rate, these peptides may be potential transmitters utilized in CNS baroreflex pathways. Moreover, alterations in CRF or bombesin transmission may underlie CNS-mediated abnormalities of baroreflex function observed in hypertension. Baroreflex function in conscious, freely-moving rats will be assessed by deriving stimulus-response curves relating changes in pulse inteval (PI) to changes of mean arterial pressure (MAP) in rats receiving CNS injections of CRF, bombesin and control solutions. This will be repeated in rats subjected to selective or combined blockade of peripheral SNS and PNS transmission. These studies will determine whether CFR and bombesin modulate baroreflex function via baroreceptor-dependent of -independent CNS pathways and whether these effects are mediated by changes in SNS or PNS outflow. To determine whether endogenous CRF and bombesin participate in the tonic regulation of baroreflex function, these studies will be repeated in rats passively immunized against these peptides and CRF and bombesin will be measured in discrete brain regions following sinoaortic denervation. The studies outlined above will be repeated in spontaneously hypertensive rats (SHR) to determine whether CRF and bombesin participate in the development of abnormal baroreflex function observed in these rats. The SHR exhibits exaggerated SNS and hormonal responses to stress and impaired baroreflex control of heart rate. CRF acts in the CNS to increase SNS outflow, stimulate release of stress hormones, and elevate MAP and heart rate, and thus may contribute to the hypertension and pronounced stress responses that characterize the SHR. The health relevancy of these studies is overt in that baroreflex function is modified by stressful stimuli and hypertension. Basic knowledge regarding the CNS transmitters involved in the regulation of baroreflex function is prerequisite to understanding possible abnormalities that underlie cardiovascular disease.

拟议研究的一般目标是检查两种神经肽，皮质激素释放因子（CRF）和bombesin，in 压力感受器反射的中枢神经系统（CNS）调节。血压的压力反射控制主要通过交感神经（SNS）和副交感神经（PNS）的调整到心脏和脉管系统。由于CRF和Bombesin对CNS采取了深刻的行动影响SNA和PNS活动，血压和心率，这些肽可能是CNS BaroreFlex中使用的潜在发射器途径。此外，CRF或Bombesin传播的改变可能 CNS介导的基础降压功能异常高血压。有意识的，自由移动的大鼠的BaroreFlex功能将由得出有关脉冲内膜（PI）的变化的刺激反应曲线接受中枢神经系统注射大鼠的平均动脉压（MAP）的变化 CRF，孟买和控制解决方案。这将在大鼠中重复受到外围SN和PN的选择性或组合的封锁传播。这些研究将确定CFR和Bombesin是否通过非依赖性CNS的压力感受器依赖性CNS调节压力反射函数途径以及这些效果是否是由SNS或PN的变化介导的外流。确定内源性CRF和Bombesin是否参与 Baroreflex功能的补品调节，将重复这些研究在对这些肽和CRF和Bombesin的被动免疫的老鼠中将在中质神经区神经后在离散的大脑区域中进行测量。上面概述的研究将在自发的高血压中重复大鼠（SHR）确定CRF和Bombesin是否参与在这些大鼠中观察到的异常压力反射功能的发展。这 SHR表现出夸张的SNS和对压力和受损的荷尔蒙反应心率的压力反射控制。 CRF在中枢神经系统中起作用以增加SNS 流出，刺激应力激素的释放，并提升地图和心脏速率，因此可能导致高血压和明显的压力特征SHR的响应。这些研究的健康相关性是公开的通过压力刺激和高血压来改变。基本知识关于涉及压力反射调节的中枢神经系统发射器功能是理解可能异常的先决条件心血管疾病基础。