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AVP MODULATION OF CARDIOVASCULAR RESPONSE TO EXCERCISE

AVP 对运动的心血管反应的调节

基本信息

批准号：
2637988
负责人：
CHARLES L STEBBINS
金额：
$ 16.4万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-01-01 至 1999-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2637988
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

项目摘要

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）确定后肢的电诱导静态收缩引起脊髓和全身AVP增加。如果是这样，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，背角和血浆水平将在休息时和收缩前后测量AVP的浓度。（2）探讨肌纤维切断的可能性; 肌肉收缩期间全身释放的AVP有助于通过其对动脉压力感受器反射的作用而与运动加压反射相关联。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和肾脏的变化响应静态收缩交感神经活动（RSNA）将在恒定的颈动脉窦压力下进行评估。答复将比较系统性AVP受体抑制前后，最后区，或选择性AVP受体阻滞剂在最后区。最后区中的AVP阻断将通过微量注射特异性AVP受体拮抗剂;（3）确定AVP是否在脊髓背角对运动加压反射的衰减作用因此，对血管的升压和收缩反应，静态收缩将在适当的前后进行监测鞘内注射AVP或其受体拮抗剂或微量注射注射到脊髓的背角的结果这些研究将有助于确定潜在的作用机制， AVP对心血管系统在运动中，并可能使医生以改变该肽在可能有害的条件下的作用（高血压、心力衰竭或缺血性心脏病）。