Methionine sulfoxide reductase-A (MsrA) reverses oxidation of methionine residues, thereby protecting against oxidative stress in disease and aging . A physiological role of MsrA-dependent redox signaling in modulation of neuronal excitability has been suggested from in vitro studies [2,3], but in vivo evidence is lacking. We tested the hypothesis that MsrA-dependent redox signaling contributes to normal autonomic regulation in young, healthy mice. Blood pressure (BP), heart rate (HR) and locomotor activity were measured in young (10–12 wk) MsrA deficient (−/−) (n=6) and control C57BL/6 (n=7) mice by radiotelemetry. Baroreflex sensitivity (BRS, sequence technique), HR variability (HRV, SD-pulse intervals), and cardiac vagal and sympathetic tone (HR responses to methylatropine and propranolol) were measured. Compared with control mice, MsrA−/− mice exhibited increases in mean 24-h BP (122±4 vs. 112±2 mm Hg) and HR (624±11 vs. 594±8 bpm) (P<0.05), despite decreased activity (4±1 vs. 10±2 counts/min). BRS (0.8±0.1 vs. 2.2±0.1 ms/mm Hg), HRV (4.2±1.8 vs. 12.3±6.0 ms), and cardiovagal tone (+26±5 vs. +119±15 bpm) were markedly reduced in MsrA−/− mice (P<0.05), while sympathetic tone was increased significantly (−137±13 vs. −86±5 bpm). We conclude that young MsrA−/− mice exhibit severe autonomic dysregulation with decreased BRS, decreased cardiovagal tone, increased sympathetic tone, and hypertension. Thus, MsrA is required for normal baroreflex sensitivity and sympathovagal balance. Increasing MsrA expression at appropriate sites may provide a novel therapeutic approach for restoring baroreflex sensitivity in disease and aging.
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© 2010 Published by Elsevier Inc.