SUPRABULBAR EFFECTS OF SINOAORTIC DENERVATION

去主动脉神经的球上效应

• 批准号: 3343886
• 负责人: NATALIE ALEXANDER
• 金额: $ 11.86万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3343886
• 关键词: baroreceptors; body movement; caudate nucleus; denervation; dopamine; experimental brain lesion; neuroanatomy; neurochemistry; neurogenic hypertension; substantia nigra; supraoptic nucleus; tyrosine 3 monooxygenase; vasopressins

The sinoaortic denervated (SAD) rat has mild hypertension and labile arterial pressure associated with body movements and haselevated plasma vasopressin. Recent investigations revealed that tyrosine hydroxylase (TH) activity and dopamine (DA) concentration were reduced in the caudate nucleus of SAD rats and that TH activity was also reduced in substantia nigra and supraoptic nucleus (SON). Since the nigrostriatal system is a major site of somatomotor neural integration and since centrally active DA agonists have a blood pressure lowering effect in some forms of hypertension, the hypothesis will be tested that reduced DA metabolism in the nigrostriatum causes the characteristic body movement- related pressure lability of SAD rats and contributes to their mild hypertension. Microinjections of DA agonists will be made into the nigrostriatum of freely moving SAD and sham-operated control rats whose arterial pressure and heart rate are being continuously recorded. An on-line DEC computer will generate frequency-interval histograms, mean and standard deviation values of pressure and heart rate. Hemodynamic effects of lesioning nigrostriatal region of normal rats will also be evaluated. Another hypothesis to be tested is that reduced synthesis and release of catecholamines in the hypothalamus disinhibits vasopressin secretion in SAD rats. In vivo and in vitro TH activity, release and turnover of catecholamines in SON and paraventricular nucleus will be measured. The time of onset and duration of biochemical changes in both nigrostriatal and hypothalamic regions will be studied. Onset of changes in caudate also will be evaluated by in vivo voltammetry which, in pilot studies, indicated DA was released by sinoaortic denervation. All biochemical assays will be sensitive, specific and radioisotopic. Finally immunohistofluorescent probes will be used to look for evidence of projections between brain stem areas associated with cardiovascular regulation and the substantia nigra.

去主动脉神经 (SAD) 大鼠患有轻度高血压且不稳定 与身体运动和血浆升高相关的动脉压 加压素。 最近的研究表明，酪氨酸羟化酶（TH） 尾状核的活动和多巴胺 (DA) 浓度降低 SAD 大鼠的细胞核，实质内 TH 活性也降低 黑质和视上核（SON）。 由于黑质纹状体系统是 躯体运动神经整合的主要部位以及中枢活跃的 DA 激动剂在某些形式中具有降低血压的作用 高血压，将检验以下假设：DA 代谢减少 黑质纹状体引起与身体运动相关的特征性压力 SAD 大鼠的不稳定性并导致其轻度高血压。 将 DA 激动剂显微注射到黑质纹状体中 自由活动的 SAD 大鼠和假手术对照大鼠的动脉压 和心率被连续记录。 在线 DEC 计算机 将生成频率间隔直方图、平均值和标准差 压力和心率值。 病变的血流动力学影响 还将评估正常大鼠的黑质纹状体区域。 其他 要检验的假设是减少合成和释放 下丘脑中的儿茶酚胺会抑制 SAD 患者的加压素分泌 老鼠。 体内和体外 TH 活性、释放和周转 将测量 SON 和室旁核中的儿茶酚胺。 这 黑质纹状体和黑质纹状体生化变化的发生时间和持续时间 将研究下丘脑区域。 尾状核也开始发生变化 将通过体内伏安法进行评估，在试点研究中表明 DA 通过去主动脉神经释放。 所有生化检测均将 敏感、特异和放射性同位素。 最后进行免疫组化荧光 探针将用于寻找脑干之间投射的证据 与心血管调节和黑质相关的区域。