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: 2219738
• 负责人: BARRY R DWORKIN
• 金额: $ 15.75万
• 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: 1989-04-15 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2219738
• 关键词: afferent nerve; auditory discrimination; baroreflex; bradycardia; cardiovascular system; electrostimulus; laboratory rat; mathematical model; neural information processing; neural plasticity; operant conditionings; phenylephrine; vascular smooth muscle nervous control; vasoconstriction

Within the cardiovascular system the baroreflexes of the carotid sinus and aortic arch are crucial to blood pressure stabilization. The experiments proposed will determine whether a mechanism of neural plasticity, known as classical conditioning, which is involved in drug tolerance, digestive secretion, and setting the gain of critical visual tracking reflexes, is also involved in calibration of the baroreflexes. Classical conditioning itself is simply a repeating sequence of a weak (conditioned) stimulus followed by a stronger (unconditioned) stimulus. It has been known since Pavlov that with this procedure eventually the weaker stimulus produces reflex effects resembling those of the stronger stimulus. Recent mathematical models describe how classical conditioning can significantly augment the effectiveness of innate regulatory reflexes and in various ways tailor them to the needs of an individual's anatomy, constitution and life experience. The human cardiac baroreflex can be classically conditioned, and preliminary studies in rats show that the vascular sympathoinhibitory effect of the baroreflex can also be readily conditioned. The proposed experiments all use the same unique long-term behavioral-physiological rat model to (1) determine if a widely observed, but poorly understood phenomenon, shock conditioned vagal bradycardia, is in reality a case of implicit baroreflex conditioning; (2) verify and extend preliminary evidence that the vascular baroreflex can be classical conditioned; (3) examine and analyze a distinctive 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 mathematical models of regulation using actual carotid sinus cul de sac pressures as the conditioning stimuli. The proposed project has the following implications for improving health and treating disease: (a) In a conventional social setting the cardiovascular responses to stress, such as blood pressure elevation, are frequently inappropriate to the physiological needs of impending behavior. With time, repetition of these unnecessary "emergency" responses may contribute to increased risk of an acute cardiovascular event. Conditioned bradycardia that develops with repeated exposures to stress may itself be, or be a useful model for, an important homeostatic function; understanding its basis may help explain why for some people compensatory cardiovascular responses to stress fail to develop in a normal manner, and suggest behavioral or pharmacological interventions to facilitate more appropriate responses. (b) Basic studies extending the experimental model and control theory concepts of traditional baroreflex physiology to include classical conditioning, will show how conditioning plays an important role in natural cardiovascular adjustments. By thus highlighting a novel and unappreciated mechanism of cardiovascular regulation, this work could open unexplored, potentially fruitful, avenues for research on the control of blood pressure.

在心血管系统中，颈动脉窦的压力反射 主动脉弓对血压稳定至关重要。 这 提出的实验将确定神经的机制是否 可塑性，称为经典条件，参与药物 耐受性，消化分泌，并设定关键视觉的增长 跟踪反射，也参与了压力反射的校准。 经典条件本身只是弱的重复顺序 （条件）刺激，然后是更强（无条件的）刺激。 自Pavlov以来就已经知道，随着此过程，最终 较弱的刺激产生反射效应，类似于强度 刺激。 最近的数学模型描述了古典条件 可以显着提高先天监管反射的有效性 并以各种方式根据个人解剖学的需求量身定制它们 宪法和生活经验。 人类心脏弱反应可以经典的条件，并且 大鼠的初步研究表明血管交感神经抑制性 也很容易调理压力反射的效果。 提议 实验都使用相同独特的长期行为生理学 大鼠模型到（1）确定是否广泛观察到但知之甚少 现象，震动的迷走性心动过缓，实际上是 隐式巴罗诺克体调节； （2）验证并扩展初步 有证据表明血管压力反射可以是经典的条件； （3） 检查和分析一种独特的条件形式，尤其是 与BaroreFlex的自然校准有关，其中较弱和 更强的调理刺激都应用于压力感受器。和 （4）严格测试生物学假设和预测准确性 使用实际的颈动脉窦Cul de Sac进行调节的数学模型 压力作为调节刺激。 拟议的项目对改善健康有以下含义 和治疗疾病：（a）在常规社会环境中 心血管对压力的反应，例如血压升高，是 通常不适合即将来临的生理需求 行为。 随着时间的流逝，重复这些不必要的“紧急” 反应可能导致急性心血管的风险增加 事件。 条件性心动过缓，并反复暴露于 压力本身可能是或成为重要的模型 功能;了解它的基础可能有助于解释为什么对某些人 补偿性心血管对压力的反应无法在 正常方式，并建议行为或药理干预措施 促进更适当的回应。 （b）扩展的基础研究 实验模型和控制理论的传统巴罗雷弗莱克体的概念 生理学要包括经典条件，将显示如何调理 在自然心血管调节中起着重要作用。 这样 突出了一种新颖的心血管机制 法规，这项工作可能打开未开发的，潜在的富有成果， 研究血压控制的途径。