Increased heart rate variability in mice overexpressing the Cu/Zn superoxide dismutase.
Cu/Zn superoxide dismutase (SOD1) is implicated in various pathological conditions including Down's syndrome, neurodegenerative diseases, and afflictions of the autonomic nervous system (ANS). To assess the SOD1 contribution to ANS dysfunction, especially its influence on cardiac regulation, we studied the heart rate variability (HRV) and cardiac arrhythmias in conscious 12-month-old male and female transgenic mice for the human SOD1 gene (TghSOD1). TghSOD1 mice presented heart rate reduction as compared with control FVB/N individuals. All HRV parameters reflecting parasympathetic activity were increased in TghSOD1. Pharmacological studies confirmed that the parasympathetic tone was exacerbated and the sympathetic pathway was functional in TghSOD1 mice. A high frequency of atrioventricular block and premature ventricular contractions was observed in TghSOD1. By biochemical assays we found that SOD1 activities were multiplied by 9 and 4 respectively in the heart and brainstem of transgenic mice. A twofold decrease in cholinesterase activity was observed in the heart but not in the brainstem. We demonstrate that SOD1 overexpression induces an ANS dysfunction by an exacerbated vagal tone that may be related to impaired cardiac activity of the cholinesterases and may explain the high occurrence of arrhythmias.
Centre National de Recherche Scientifique, Unité Mixte de Recherche 6542 Laboratoire de Physiologie des Cellules Cardiaques et Vasculaires, Université François-Rabelais, Tours, France.
Jérôme
J
Thireau
Denise
D
Poisson
Bei Li
BL
Zhang
Ludovic
L
Gillet
Marie
M
Le Pécheur
Christian
C
Andres
Jacqueline
J
London
Dominique
D
Babuty
D000818:Animals; D001933:Brain Stem / Q000201:enzymology; D002802:Cholinesterases / Q000378:metabolism; D002940:Circadian Rhythm; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000201:enzymology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D013482:Superoxide Dismutase; D002802:Cholinesterases