title: Cardiovascular dysfunction associated with neurodegeneration in an experimental model of Parkinson's disease.
abstract: Patients with Parkinson's disease (PD) exhibit both motor and non-motor symptoms. Among the non-motor symptoms, cardiovascular autonomic dysfunction is frequently observed. Here, we evaluated baroreflex function, vascular reactivity and neuroanatomical changes in brainstem regions involved in the neural control of circulation in the 6-hydroxydopamine (6-OHDA) model of PD. Male Wistar rats received a bilateral injection of 6-OHDA or vehicle into the striatum. After 61days, baroreflex function and vascular reactivity were assessed. The 6-OHDA and vehicle groups showed similar increases in mean arterial pressure (MAP) in response to phenylephrine (PE). However, the bradycardia observed in the vehicle group was blunted in the 6-OHDA-treated rats. Injection of sodium nitroprusside (SNP) decreased hypotension, tachycardia and vascular relaxation in 6-OHDA-treated rats. Bilateral intrastriatal 6-OHDA led to massive degeneration of tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra and to reductions in the numbers of A1/C1 and A5 catecholaminergic neurons while sparing A2 neurons within the nucleus of the solitary tract (NTS). 6-OHDA-treated rats also showed decreases in Phox2b-expressing neurons in the NTS and in choline acetyltransferase (ChAT) immunoreactivity in the nucleus ambiguus. Altogether, our data suggest that this model of PD includes neuroanatomical and functional changes that lead to cardiovascular impairment.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Barbara
authors.initials: B
authors.lastname: Falquetto
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: Tuppy
authors.affiliation: Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP-Univ. Estadual Paulista, 16015-050 Araçatuba, SP, Brazil.
authors.forename: Simone R
authors.initials: SR
authors.lastname: Potje
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Moreira
authors.affiliation: Department of Basic Sciences, School of Dentistry of Araçatuba, UNESP-Univ. Estadual Paulista, 16015-050 Araçatuba, SP, Brazil.
authors.forename: Cristina
authors.initials: C
authors.lastname: Antoniali
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, 05508-000 São Paulo, SP, Brazil. Electronic address: takakura@icb.usp.br.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Takakura
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001341:Autonomic Nervous System / Q000473:pathology / Q000503:physiopathology; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D001919:Bradycardia / Q000473:pathology / Q000503:physiopathology; D001933:Brain Stem / Q000473:pathology / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009599:Nitroprusside; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology*; D017208:Rats, Wistar; D013610:Tachycardia / Q000473:pathology / Q000503:physiopathology; D046509:Tissue Culture Techniques; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D009599:Nitroprusside; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D000109:Acetylcholine
keywords: Baroreflex sensitivity; Brainstem; Parkinson disease; Vascular reactivity