AVP MODULATION OF CARDIOVASCULAR RESPONSE TO EXCERCISE

AVP 对运动的心血管反应的调节

• 批准号: 2224437
• 负责人: CHARLES L STEBBINS
• 金额: $ 14.18万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2224437
• 关键词: area postrema; autoradiography; baroreceptors; baroreflex; cardiovascular pharmacology; carotid sinus; cats; denervation; dorsal horn; hormone regulation /control mechanism; microdialysis; muscle contraction; neural transmission; neurohypophysis; neuropharmacology; striated muscles; sympathetic nervous system; vasopressins

This research will determine the role of AVP in modulating the cardiovascular response to exercise in cats. Specific aims are: (1) to determine if electrically-induced static contraction of the hindlimb induces increases in spinal and systemic AVP. If this is the case, we will ascertain if these responses are due, in part, to a contraction- induced neuroendocrine reflex. Consequently, dorsal horn and plasma levels of AVP will be measured at rest and during contraction before and after denervation of the contracting muscle; (2) to investigate the possibility that AVP, released systemically during muscular contraction, contributes to the exercise pressor reflex by its action on the arterial baroreflex. Precisely, the possibility that AVP sensitizes the arterial baroreceptors during exercise will be examined. Thus, changes in MAP and renal sympathetic nerve activity (RSNA) in response to static contraction will be evaluated at a constant carotid sinus pressure. Responses will be compared before and after systemic AVP receptor inhibition, lesion of the area postrema, or selective AVP receptor blockade in the area postrema. AVP blockade in the area postrema will be induced by microinjections of specific AVP receptor antagonists; (3) to determine if AVP acts within the spinal dorsal horn to attenuate the exercise pressor reflex by modulation of its afferent arm. Therefore, the pressor and contractile responses to static contraction will be monitored before and after appropriate intrathecal injection of AVP or its receptor antagonists or microinjection of these drugs into the dorsal horn of the spinal cord. The results of these studies will help identify the mechanisms underlying the action of AVP on the cardiovascular system during exercise and may allow physicians to modify the action of this peptide in conditions where it may be harmful (hypertension, heart failure, or ischemic heart disease).

这项研究将确定 AVP 在调节 猫对运动的心血管反应。具体目标是：（1） 确定后肢是否由电引起静态收缩 诱导脊髓和全身 AVP 增加。 如果是这样的话，我们 将确定这些反应是否部分归因于收缩- 诱发神经内分泌反射。因此，背角和血浆水平 AVP 将在休息前和收缩前和收缩后测量 收缩肌肉的去神经支配； (2) 考察可能性 AVP 在肌肉收缩期间全身释放，有助于 通过对动脉压力反射的作用来锻炼升压反射。 准确地说，AVP 使动脉压力感受器敏感的可能性 运动期间将进行检查。因此，MAP 和肾脏的变化 交感神经活动（RSNA）响应静态收缩将 在恒定的颈动脉窦压力下进行评估。回应将是 比较全身 AVP 受体抑制前后， 后区，或选择性 AVP 受体阻断后区。 显微注射可诱导 AVP 阻断后部区域 特异性AVP受体拮抗剂； (3) 确定AVP是否在范围内起作用 脊髓背角通过调制减弱运动加压反射 它的传入臂。因此，加压和收缩反应 在适当的前后将监测静态收缩 AVP或其受体拮抗剂鞘内注射或显微注射 这些药物进入脊髓的背角。结果 这些研究将有助于确定其作用的机制 运动期间 AVP 对心血管系统的影响可能允许医生 在可能有害的情况下改变该肽的作用 （高血压、心力衰竭或缺血性心脏病）。