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Calorie restriction as a new approach for resetting carotid body chemoreflex control in heart failure (873.11)
Author(s) -
Del Rio Rodrigo,
Marcus Noah,
Schultz Harold
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.873.11
Subject(s) - medicine , endocrinology , carotid body , chemoreceptor , heart failure , hypoxia (environmental) , sod2 , oxidative stress , chemistry , superoxide dismutase , stimulation , oxygen , receptor , organic chemistry
The carotid body (CB) plays a pivotal role in the increased chemosensitivity following chronic heart failure (CHF). The mechanisms underlying the CB potentiation in CHF are not fully understood. However, it is known that oxidative stress contributes to the exaggerated CB function. Since calorie restriction (CR) has been shown to reduce oxidative stress we hypothesized that CR normalizes CB afferent activity and restores normal chemoreflex drive in CHF. Male rats (200g) were subjected to coronary artery ligation or sham surgery. CHF and sham animals were randomly allocated into 2 groups: Ad libitum calorie intake (AL) or CR (30% less caloric intake compared to AL). Ventilatory chemoreflex responses to hypoxia (FiO2~10%) were measured 4 weeks after AL or CR. CB chemoreceptor afferent neural activity was recorded and Mn‐superoxide dismutase (SOD2) protein expression was assessed in CB chemoreceptor cells. CHF‐AL rats compared to sham‐AL rats displayed exaggerated ventilatory chemoreflex response to hypoxia, potentiation of CB afferent discharge, and reduced SOD2 expression in CB chemoreceptor cells (21±1 vs. 73±3 a.u., CHF‐AL vs. sham‐AL, p<.05). CR reduced ventilatory chemoreflex function in CHF rats to levels comparable to the ones obtained in sham‐AL rats. CR in sham rats had no effect on chemoreflex function. Compared to CHF‐AL rats, CHF‐CR rats displayed reduced CB afferent discharge during hypoxia (150±13 vs. 262±21 Hz, CHF‐CR vs. CHF‐AL, p<.05) and a 3‐fold increase in SOD2 protein expression in CB chemoreceptor cells. Our results show that CR increases SOD2 expression in CB chemoreceptor cells, prevents abnormal CB afferent function, and normalizes chemoreflex control in CHF rats. Grant Funding Source : Supported by NIH PO1‐HL62222