Abstract 1377: Vagal Stimulation Suppresses Reactive Oxygen Species (ROS) in the Failing Myocardium in Mice
Background: Redox alterations play a major role in the pathogenesis of heart failure. Since vagal nerve stimulation (VNS) is known to improve survival and attenuate cardiac remodeling in heart failure (Circulation 2004), we hypothesized that the vagally-mediated redox regulation may account for those beneficial effects.
Methods and Results: In mice we created myocardial infarction (MI) by ligating the left coronary artery. Mice that survived 28 days after MI were used as a model of chronic heart failure (CHF). We stimulated the right vagal nerve in CHF and Sham mice for 15 minutes and measured the redox status using in vivo ESR. As can be seen in the figure, the signal decay rate of nitroxide probe, an index of redox status, was enhanced in CHF compared with Sham, and was fully antagonized by VNS. Atropine nullified the impact of VNS on ROS production. VNS markedly decreased cardiac tissue norepinephrine (NE) (0.60 ± 0.12 vs. 0.25 ± 0.07 ng/mL, n = 6, p < 0.05). In neonatal cardiomyocytes, NE dose-dependently induced ROS, whereas acetylcholine (10 μmol/L) suppressed the NE (10 μmol/L) induced ROS (3.7 ± 0.5 vs. 2.5 ± 0.3/control, n = 12, p < 0.05).
Conclusions: VNS modulates the cardiac redox status and adrenergic drive via the muscarinic receptor activation, and suppressed ROS in failing hearts.