Document Detail


Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion.
MedLine Citation:
PMID:  23519622     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ming Zhao; Xi He; Xue-Yuan Bi; Xiao-Jiang Yu; W Gil Wier; Wei-Jin Zang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-22
Journal Detail:
Title:  Basic research in cardiology     Volume:  108     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-03-22     Completed Date:  2013-08-16     Revised Date:  2014-08-20    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  345     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / metabolism*
Animals
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelium, Vascular / metabolism,  pathology,  physiopathology
Inflammation / metabolism,  pathology,  physiopathology,  prevention & control*
Inflammation Mediators / blood
Interleukin-1beta / blood
Male
Mesenteric Artery, Superior / drug effects,  metabolism*,  pathology,  physiopathology
Microdialysis
Myocardial Infarction / metabolism,  pathology,  physiopathology,  prevention & control*
Myocardial Reperfusion Injury / metabolism,  pathology,  physiopathology,  prevention & control*
NF-kappa B / metabolism
Nicotinic Antagonists / pharmacology
Phosphorylation
Rats
Rats, Sprague-Dawley
Receptor, Muscarinic M3 / drug effects,  metabolism
Receptors, Nicotinic / drug effects,  metabolism*
STAT3 Transcription Factor / metabolism
Time Factors
Tissue Culture Techniques
Tumor Necrosis Factor-alpha / blood
Vagus Nerve Stimulation*
Vascular Diseases / metabolism,  pathology,  physiopathology,  prevention & control*
Vasoconstriction
Vasoconstrictor Agents / pharmacology
Vasodilation
Vasodilator Agents / pharmacology
alpha7 Nicotinic Acetylcholine Receptor
Chemical
Reg. No./Substance:
0/Chrna7 protein, rat; 0/Inflammation Mediators; 0/Interleukin-1beta; 0/NF-kappa B; 0/Nicotinic Antagonists; 0/Receptor, Muscarinic M3; 0/Receptors, Nicotinic; 0/STAT3 Transcription Factor; 0/Stat3 protein, rat; 0/Tumor Necrosis Factor-alpha; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 0/alpha7 Nicotinic Acetylcholine Receptor; N9YNS0M02X/Acetylcholine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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