Attenuated baroreflex in a Parkinson's disease animal model coincides with impaired activation of non-C1 neurons.

Abstract

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 60days, 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.