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01-05-2013 | Original Contribution

Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion

Authors: Ming Zhao, Xi He, Xue-Yuan Bi, Xiao-Jiang Yu, W. Gil Wier, Wei-Jin Zang

Published in: Basic Research in Cardiology | Issue 3/2013

Abstract

Myocardial ischemia/reperfusion (I/R) induces inflammatory response that may lead to remote vascular injury. Vagal nerve elicits the cholinergic anti-inflammatory pathway by activating α7 nicotinic acetylcholine receptors (α7nAChR). Nevertheless, the role of vagal nerve-mediated anti-inflammatory pathway in the vasculature has not been studied previously. Therefore, we aimed to clarify the potential role of vagal stimulation (VNS) in regulating remote vascular injury after myocardial I/R. Adult male Sprague–Dawley rats were subjected to VNS starting 15 min prior to ischemia until the end of reperfusion. VNS not only reduced infarct size and improved cardiac function, but also ameliorated myocardial I/R-induced dysfunctional vasoconstriction and vasodilatation and degradation of endothelial structure in mesenteric arteries. VNS decreased serum and vascular levels of tumor necrosis factor-α and IL-1β. Interestingly, in vivo microdialysis studies demonstrated that VNS increased ACh concentration in the mesenteric circulation. Furthermore, VNS up-regulated expressions of muscarinic ACh receptors-3 (M₃AChR) and α7nAChR in mesenteric arteries. Preserved endothelial relaxations by VNS were inhibited by atropine or methyllycaconitine, indicating that functional protection was associated with M₃ and α7nAChR activation. Finally, VNS increased STAT3 phosphorylation and inhibited NF-κB activation in mesenteric arteries, and these effects were abolished by α7nAChR shRNA treatment, indicating VNS-mediated anti-inflammatory effect mainly involved α7nAChR. These results demonstrated for the first time that VNS protected against remote vascular dysfunction, through the cholinergic anti-inflammatory pathway which is dependent on α7nAChR. Our findings represent a significant addition to the understanding of vagal nerve-mediated pathways and the potential roles they play in regulating the vasculature.

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Title: Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion
Authors: Ming Zhao
Xi He
Xue-Yuan Bi
Xiao-Jiang Yu
W. Gil Wier
Wei-Jin Zang
Publication date: 01-05-2013
Publisher: Springer-Verlag
Published in: Basic Research in Cardiology / Issue 3/2013
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-013-0345-1

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Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion

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