Cabral Laís M, Moreira Thiago S, Takakura Ana C, Falquetto Bárbara
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil.
Auton Neurosci. 2020 May;225:102655. doi: 10.1016/j.autneu.2020.102655. Epub 2020 Feb 15.
Orthostatic hypotension is one of the most common symptoms observed in Parkinson's disease (PD), a neurodegenerative disease caused by death of dopaminergic neurons in the substantia nigra pars compacta (SNc), and it is associated with denervation of the heart and impairment of the baroreflex. Here, we aimed to investigate if the impaired baroreflex was associated with lower activation of cardiovascular brainstem areas in a 6-hydroxydopamine (6-OHDA) animal model of PD. The PD model was generated with male Wistar rats by injection of 6-OHDA or vehicle into the striatum. After 20 or 60 days, the femoral vein and artery were cannulated to assess cardiovascular parameters during injection of sodium nitroprusside (SNP) or phenylephrine (Phe). Brainstem slices were submitted to immunohistochemistry and immunofluorescence. After 6-OHDA injection, 75% of the dopaminergic neurons in the SNc were absent, confirming establishment of the PD model. Intravenous (iv) injection of SNP generated reduced hypotension and tachycardia response, and the noncatecholaminergic (nonC1) neurons of the rostral ventrolateral medulla (RVLM) were less activated. Additionally, iv injection of Phe increased blood pressure and bradycardia to the same extent and activated equivalent numbers of neurons in the nucleus of the solitary tract and the caudal ventrolateral medulla as well as cholinergic neurons of the dorsal motor nucleus of the vagus and the nucleus ambiguus between control and PD animals. In summary, these data showed that in the PD model, impairment of cardiovascular autonomic control was observed only during deactivation of the baroreflex, which could be related to reduced activation of non-C1 neurons within the RVLM.
直立性低血压是帕金森病（PD）中最常见的症状之一，帕金森病是一种由黑质致密部（SNc）多巴胺能神经元死亡引起的神经退行性疾病，它与心脏去神经支配和压力反射受损有关。在此，我们旨在研究在6-羟基多巴胺（6-OHDA）诱导的帕金森病动物模型中，压力反射受损是否与心血管脑干区域的激活降低有关。通过向雄性Wistar大鼠纹状体内注射6-OHDA或溶剂来建立帕金森病模型。20天或60天后，将股静脉和动脉插管，以评估注射硝普钠（SNP）或去氧肾上腺素（Phe）期间的心血管参数。将脑干切片进行免疫组织化学和免疫荧光检测。注射6-OHDA后，SNc中75%的多巴胺能神经元缺失，证实帕金森病模型建立成功。静脉注射SNP后，低血压和心动过速反应减弱，延髓头端腹外侧区（RVLM）的非儿茶酚胺能（nonC1）神经元激活减少。此外，静脉注射Phe后，对照组和帕金森病动物的血压升高和心动过缓程度相同，孤束核、延髓尾端腹外侧区的神经元激活数量相当，迷走神经背核和疑核的胆碱能神经元激活数量也相当。总之，这些数据表明，在帕金森病模型中，仅在压力反射失活期间观察到心血管自主控制受损，这可能与RVLM内non-C1神经元的激活减少有关。
