Vagal nerve stimulation reduces metabolic rate and uncouples the relationship between heart rate and oxygen consumption in conscious mice (LB775)

Abstract

We tested the hypothesis that an increase in metabolic rate contributes to the weight loss associated with chronic vagal nerve stimulation (VNS) that has been observed in patients with epilepsy or depression and in animal studies. Blood pressure (BP) sensors (DSI) and cervical vagal nerve stimulators were implanted in C57Bl6 mice (n=5). On the following day, arterial BP, heart rate (HR), oxygen consumption (VO2), and respiratory exchange rate (RER) were recorded in conscious mice during application of different VNS intensities (3V, max. current 1mA, 1ms pulses at frequencies ranging from 1 Hz to 10 Hz in steps of 1 Hz, randomized order). Each VNS intensity was applied for 20 min and preceded by a baseline (20 min). In average (all VNS intensities pooled), VNS reduced HR (374±37 vs. 504±14 bpm, P<0.05), mean BP (95±5 vs. 107±8 mmHg, P<0.05), and VO2 (1,556±231 vs. 2,201±178 mL/kg/h, P<0.05) but did not alter RER (0.85±0.09 vs. 0.77±0.03). The significant linear correlation between HR and VO2 during baseline without VNS (R2: 0.34±0.08) was lost during VNS (R2: 0.06±0.03). These data suggest that an increase in metabolic rate does not contribute to weight loss associated with chronic VNS. Furthermore, VNS uncouples the linear relationship between HR and VO2. We speculate that VNS may shift energy homeostasis to a “starvation‐like” mode that is associated with reduced food intake and, subsequently decreased metabolic rate.