Augmented fear bradycardia in rats with heart failure
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In congestive heart failure (CHF), while resting parasympathetic activity becomes reduced, parasympathetically-mediated responses to stressors have not been described. This study aimed to (1) elucidate the effect of CHF on fear bradycardia, a parasympathetically-mediated response, and (2) examine if brain oxidative stress of CHF mediates fear bradycardia. White noise sound (WNS) exposure to conscious rats induced freezing behavior and elicited bradycardia. WNS exposure-elicited bradycardia was greater in rats with CHF than in controls. Superoxide dismutase mimetics administered in the lateral/ventrolateral midbrain periaqueductal gray (l/vlPAG), a region that contributes to the generation of fear bradycardia, had no effect on the bradycardia response in control and CHF rats. Dihydroethidium staining in situ showed that superoxide generation in the l/vlPAG of CHF rats was increased as compared to controls. These results demonstrate that CHF leads to the augmentation of fear bradycardia. Moreover, oxidative stress in the l/vlPAG of CHF unlikely mediates the augmented fear bradycardia.
KeywordsFear Heart failure Heart rate Parasympathetic nervous system Midbrain periaqueductal gray
We thank Yumiko Inoue for assistance in rat echocardiography, and Ryo Inoue for assistance in rat coronary artery ligation surgery. This study was financially supported by JSPS KAKENHI 26670112 (to SK) and 15H05367 (to SK).
SK designed research, performed experiments, analyzed the data, prepared the figures, interpreted the results, and drafted, edited, and revised the manuscript. IH and TW interpreted the results and revised the manuscript critically for important intellectual content.
Compliance with ethical standards
Conflict of interest
The authors declare no competing interests and no relationship that may lead to any conflict of interest.
All procedures outlined in this study complied with the Guiding Principles for the Care and Use of Animals in the Fields of Physiological Sciences of the Physiological Society of Japan, and were approved by the Animal Care Committee of Tottori University (Reference number: 13-Y-47).
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