CONTROL OF VASCULAR TONE BY CONTINGENT CNS STIMULATION

通过偶然的中枢神经系统刺激来控制血管张力

• 批准号: 2901110
• 负责人: BARRY R DWORKIN
• 金额: $ 16.38万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2901110
• 关键词: afferent nerve; baroreflex; behavioral /social science research tag; blood pressure; conditioning; electrostimulus; laboratory rat; mathematical model; neural plasticity; neuroregulation; vascular resistance; vascular smooth muscle nervous control; vasomotion

DESCRIPTION: (Adapted from the application) The carotid and aortic barorefleces of the cardiovascular system are crucial to blood pressure stabilization. The proposed experiments will determine whether a mechanism of neural plasticity, known as classical conditioning, important to drug tolerance, digestion, and critical visual tracking reflexes, is also involved in activation and calibration of the baroreflexes. Classical conditioning is simply a repeating sequence of a weak (conditioned) stimulus followed by a stronger (unconditioned) stimulus. It has been known, since Pavlov, that eventually, the weaker stimulus produces reflex effects closely resembling those of the stronger stimulus. Newly formulated mathematical models predict that classical conditioning can significantly augment the effectiveness of innate and life experience. The applicants recently established that the vascular sympathoinhibitory and cardiac depressor effects of the baroreflex could be conditioned, and that the conditioned responses satisfy the assumptions of the models. The present experiments use a unique, economical, long-term rat model to 1) accurately determine the cardiac and detailed regional vascular resistance effects of the unconditioned baroreflex; 2) verify and extend the analysis of the mechanism and properties of the conditioned baroreflex; 3) study a special form of conditioning, especially relevant to natural calibration of the baroreflex, wherein the weaker and stronger conditioning stimuli are both applied to the baroreceptors; and 4) rigorously test the biological assumptions and predictive accuracy of the mathematical models of regulation. The project has the following implications for improving health and treating disease: a) In a social setting, cardiovascular responses to stress, such as blood pressure elevation, are often inappropriate to the physiological needs of impending behavior; with time, these vestigial emergency responses may increase the risk of an acute cardiovascular event. An anticipatory conditioned baroreflex, which develops with repeated exposures to stress, may ameliorate the stress effects; understanding it can help explain why for some people compensatory cardiovascular responses to stress fail to develop in a normal manner, and also suggest better behavioral or pharmacological interventions to facilitate more appropriate responses. B) Basic studies will extend the empirical mechanics and theoretical concepts of traditional baroreflex physiology to include classical conditioning, and determine whether there is a fundamental and implicit role of conditioning in normal blood pressure regulation.

描述：（从应用程序改编）颈动脉和主动脉 心血管系统的灰色折叠对血压至关重要 稳定。 提出的实验将确定是否是机制 神经可塑性（称为经典条件），对药物很重要 公差，消化和关键的视觉跟踪反射，也是 参与激活和校准了压力反射。 古典 调节只是弱（条件）刺激的重复序列 然后是更强（无条件）的刺激。 自从 帕夫洛夫（Pavlov），最终，较弱的刺激会紧密产生反射效应 类似于更强的刺激。 新配制的数学 模型预测经典条件可以显着增加 先天和生活经验的有效性。 申请人最近 确定血管交感抑制性和心脏抑制剂 可以调节巴罗雷诺弗莱克体的影响，并有条件 响应满足模型的假设。 目前的实验 使用独特的，经济的长期大鼠模型至1）准确确定 心脏和详细的区域血管抵抗作用 无条件的Baroreflex； 2）验证并扩展对机制的分析 和条件性降压力的特性； 3）研究一种特殊形式 条件，特别与BaroreFlex的自然校准有关， 其中将较弱且较强的调理刺激应用于 压力感受器； 4）严格测试生物学假设和 调节数学模型的预测准确性。 项目 对改善健康和治疗疾病具有以下影响： a）在社会环境中，心血管对压力的反应，例如血液 压力升高通常不适合生理需求 即将举行的行为；随着时间的流逝，这些残留紧急回应可能 增加急性心血管事件的风险。 一个预期 有条件的BaroreFlex，并以重复暴露于压力的情况下发展， 可以改善压力效应；了解它可以帮助解释为什么 有些人补偿性心血管对压力的反应无法发展 以正常的方式，也建议更好的行为或药理 干预措施以促进更适当的回应。 b）基础研究 将扩展传统的经验力学和理论概念 巴罗诺利体面生理学以包括经典条件，并确定 条件在正常中是否具有基本和隐性的作用 血压调节。