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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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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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References

  1. Akiyama T, Yamazaki T (2000) Adrenergic inhibition of endogenous acetylcholine release on postganglionic cardiac vagal nerve terminals. Cardiovasc Res 46:531–538. doi:10.1016/S0008-6363(00)00027-4

    Article  PubMed  CAS  Google Scholar 

  2. Arnal JF, Fontaine C, Billon-Gales A, Favre J, Laurell H, Lenfant F, Gourdy P (2010) Estrogen receptors and endothelium. Arterioscler Thromb Vasc Biol 30:1506–1512. doi:10.1161/ATVBAHA.109.191221

    Article  PubMed  CAS  Google Scholar 

  3. Arnal JF, Scarabin PY, Tremollieres F, Laurell H, Gourdy P (2007) Estrogens in vascular biology and disease: where do we stand today? Curr Opin Lipidol 18:554–560. doi:10.1097/MOL.0b013e3282ef3bca

    Article  PubMed  CAS  Google Scholar 

  4. Beny JL, Nguyen MN, Marino M, Matsui M (2008) Muscarinic receptor knockout mice confirm involvement of M3 receptor in endothelium-dependent vasodilatation in mouse arteries. J Cardiovasc Pharmacol 51:505–512. doi:10.1097/FJC.0b013e31816d5f2f

    Article  PubMed  CAS  Google Scholar 

  5. Bernik TR, Friedman SG, Ochani M, DiRaimo R, Susarla S, Czura CJ, Tracey KJ (2002) Cholinergic antiinflammatory pathway inhibition of tumor necrosis factor during ischemia reperfusion. J Vasc Surg 36:1231–1236. doi:10.1067/mva.2002.129643

    Article  PubMed  Google Scholar 

  6. Brack KE, Winter J, Ng GA (2012) Mechanisms underlying the autonomic modulation of ventricular fibrillation initiation-tentative prophylactic properties of vagus nerve stimulation on malignant arrhythmias in heart failure. Heart Fail Rev. doi:10.1007/s10741-012-9314-2

    PubMed  Google Scholar 

  7. Briones AM, Salaices M, Vila E (2005) Ageing alters the production of nitric oxide and prostanoids after IL-1beta exposure in mesenteric resistance arteries. Mech Ageing Dev 126:710–721. doi:10.1016/j.mad.2005.01.006

    Article  PubMed  CAS  Google Scholar 

  8. Calvillo L, Vanoli E, Andreoli E, Besana A, Omodeo E, Gnecchi M, Zerbi P, Vago G, Busca G, Schwartz PJ (2011) Vagal stimulation, through its nicotinic action, limits infarct size and the inflammatory response to myocardial ischemia and reperfusion. J Cardiovasc Pharmacol 58:500–507. doi:10.1097/FJC.0b013e31822b7204

    Article  PubMed  CAS  Google Scholar 

  9. Cooke JP, Ghebremariam YT (2008) Endothelial nicotinic acetylcholine receptors and angiogenesis. Trends Cardiovasc Med 18:247–253. doi:10.1016/j.tcm.2008.11.007

    Article  PubMed  CAS  Google Scholar 

  10. Crockett ET, Galligan JJ, Uhal BD, Harkema J, Roth R, Pandya K (2006) Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists. BMC Clin Pathol 6:3. doi:10.1186/1472-6890-6-3

    Article  PubMed  Google Scholar 

  11. De Ferrari GM, Schwartz PJ (2011) Vagus nerve stimulation: from pre-clinical to clinical application: challenges and future directions. Heart Fail Rev 16:195–203. doi:10.1007/s10741-010-9216-0

    Article  PubMed  Google Scholar 

  12. de Jonge WJ, Ulloa L (2007) The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 151:915–929. doi:10.1038/sj.bjp.0707264

    Article  PubMed  Google Scholar 

  13. de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ, Berthoud HR, Uematsu S, Akira S, van den Wijngaard RM, Boeckxstaens GE (2005) Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6:844–851. doi:10.1038/ni1229

    Article  PubMed  Google Scholar 

  14. El-Menyar AA (2008) Cytokines and myocardial dysfunction: state of the art. J Card Fail 14:61–74. doi:10.1016/j.cardfail.2007.09.006

    Article  PubMed  CAS  Google Scholar 

  15. Elahi MM, Yii M, Matata BM (2008) Significance of oxidants and inflammatory mediators in blood of patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth 22:455–467. doi:10.1053/j.jvca.2007.12.022

    Article  PubMed  CAS  Google Scholar 

  16. Frangogiannis NG, Smith CW, Entman ML (2002) The inflammatory response in myocardial infarction. Cardiovasc Res 53:31–47. doi:10.1016/S0008-6363(01)00434-5

    Article  PubMed  CAS  Google Scholar 

  17. Fuglesteg BN, Suleman N, Tiron C, Kanhema T, Lacerda L, Andreasen TV, Sack MN, Jonassen AK, Mjos OD, Opie LH, Lecour S (2008) Signal transducer and activator of transcription 3 is involved in the cardioprotective signalling pathway activated by insulin therapy at reperfusion. Basic Res Cardiol 103:444–453. doi:10.1007/s00395-008-0728-x

    Article  PubMed  CAS  Google Scholar 

  18. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376. doi:10.1038/288373a0

    Article  PubMed  CAS  Google Scholar 

  19. Gao X, Xu X, Belmadani S, Park Y, Tang Z, Feldman AM, Chilian WM, Zhang C (2007) TNF-alpha contributes to endothelial dysfunction by upregulating arginase in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol 27:1269–1275. doi:10.1161/ATVBAHA.107.142521

    Article  PubMed  CAS  Google Scholar 

  20. Harvey RD, Belevych AE (2003) Muscarinic regulation of cardiac ion channels. Br J Pharmacol 139:1074–1084. doi:10.1038/sj.bjp.0705338

    Article  PubMed  CAS  Google Scholar 

  21. He X, Zhang HL, Zhao M, Yang JL, Cheng G, Sun L, Li DL, Jiang HK, Zhao Q, Yu XJ, Zang WJ (2011) Amlodipine ameliorates endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 38:255–261. doi:10.1111/j.1440-1681.2011.05495.x

    Article  PubMed  CAS  Google Scholar 

  22. Hulme EC, Birdsall NJ, Buckley NJ (1990) Muscarinic receptor subtypes. Annu Rev Pharmacol Toxicol 30:633–673. doi:10.1146/annurev.pa.30.040190.003221

    Article  PubMed  CAS  Google Scholar 

  23. Jimenez-Altayo F, Briones AM, Giraldo J, Planas AM, Salaices M, Vila E (2006) Increased superoxide anion production by interleukin-1beta impairs nitric oxide-mediated relaxation in resistance arteries. J Pharmacol Exp Ther 316:42–52. doi:10.1124/jpet.105.088435

    Article  PubMed  CAS  Google Scholar 

  24. Johnston GR, Webster NR (2009) Cytokines and the immunomodulatory function of the vagus nerve. Br J Anaesth 102:453–462. doi:10.1093/bja/aep037

    Article  PubMed  CAS  Google Scholar 

  25. Juhasz B, Der P, Szodoray P, Gesztelyi R, Lekli I, Bak I, Antal M, Maulik N, Tosaki A, Vecsernyes M (2007) Adrenocorticotropic hormone fragment (4–10) attenuates the ischemia/reperfusion-induced cardiac injury in isolated rat hearts. Antioxid Redox Signal 9:1851–1861. doi:10.1089/ars.2006.1535

    Article  PubMed  CAS  Google Scholar 

  26. Kakinuma Y, Ando M, Kuwabara M, Katare RG, Okudela K, Kobayashi M, Sato T (2005) Acetylcholine from vagal stimulation protects cardiomyocytes against ischemia and hypoxia involving additive non-hypoxic induction of HIF-1alpha. FEBS Lett 579:2111–2118. doi:10.1016/j.febslet.2005.02.065

    Article  PubMed  CAS  Google Scholar 

  27. Kang YM, Gao F, Li HH, Cardinale JP, Elks C, Zang WJ, Yu XJ, Xu YY, Qi J, Yang Q, Francis J (2011) NF-κB in the paraventricular nucleus modulates neurotransmitters and contributes to sympathoexcitation in heart failure. Basic Res Cardiol 106:1087–1097. doi:10.1007/s00395-011-0215-7

    Article  PubMed  CAS  Google Scholar 

  28. Kang YM, Zhang AQ, Zhao XF, Cardinale JP, Elks C, Cao XM, Zhang ZW, Francis J (2011) Paraventricular nucleus corticotrophin releasing hormone contributes to sympathoexcitation via interaction with neurotransmitters in heart failure. Basic Res Cardiol 106:473–483. doi:10.1007/s00395-011-0155-2

    Article  PubMed  CAS  Google Scholar 

  29. Kawada T, Akiyama T, Shimizu S, Kamiya A, Uemura K, Li M, Shirai M, Sugimachi M (2009) Detection of endogenous acetylcholine release during brief ischemia in the rabbit ventricle: a possible trigger for ischemic preconditioning. Life Sci 85:597–601. doi:10.1016/j.lfs.2009.08.015

    Article  PubMed  CAS  Google Scholar 

  30. Kawada T, Shimizu S, Li M, Kamiya A, Uemura K, Sata Y, Yamamoto H, Sugimachi M (2011) Contrasting effects of moderate vagal stimulation on heart rate and carotid sinus baroreflex-mediated sympathetic arterial pressure regulation in rats. Life Sci 89:498–503. doi:10.1016/j.lfs.2011.07.026

    Article  PubMed  CAS  Google Scholar 

  31. Kelly RF, Lamont KT, Somers S, Hacking D, Lacerda L, Thomas P, Opie LH, Lecour S (2010) Ethanolamine is a novel STAT-3 dependent cardioprotective agent. Basic Res Cardiol 105:763–770. doi:10.1007/s00395-010-0125-0

    Article  PubMed  CAS  Google Scholar 

  32. Khurana S, Chacon I, Xie G, Yamada M, Wess J, Raufman JP, Kennedy RH (2004) Vasodilatory effects of cholinergic agonists are greatly diminished in aorta from M3R−/− mice. Eur J Pharmacol 493:127–132. doi:10.1016/j.ejphar.2004.04.012

    Article  PubMed  CAS  Google Scholar 

  33. Kleinbongard P, Heusch G, Schulz R (2010) TNFalpha in atherosclerosis, myocardial ischemia/reperfusion and heart failure. Pharmacol Ther 127:295–314. doi:10.1016/j.pharmthera.2010.05.002

    Article  PubMed  CAS  Google Scholar 

  34. Kong SS, Liu JJ, Hwang TC, Yu XJ, Lu Y, Zang WJ (2011) Tumour necrosis factor-alpha and its receptors in the beneficial effects of vagal stimulation after myocardial infarction in rats. Clin Exp Pharmacol Physiol 38:300–306. doi:10.1111/j.1440-1681.2011.05505.x

    Article  PubMed  CAS  Google Scholar 

  35. Kong SS, Liu JJ, Hwang TC, Yu XJ, Zhao M, Zhao M, Yuan BX, Lu Y, Kang YM, Wang B, Zang WJ (2012) Optimizing the parameters of vagus nerve stimulation by uniform design in rats with acute myocardial infarction. PLoS One 7:e42799. doi:10.1371/journal.pone.0042799

    Article  PubMed  CAS  Google Scholar 

  36. Li DL, Liu JJ, Liu BH, Hu H, Sun L, Miao Y, Xu HF, Yu XJ, Ma X, Ren J, Zang WJ (2011) Acetylcholine inhibits hypoxia-induced tumor necrosis factor-alpha production via regulation of MAPKs phosphorylation in cardiomyocytes. J Cell Physiol 226:1052–1059. doi:10.1002/jcp.22424

    Article  PubMed  CAS  Google Scholar 

  37. Li M, Zheng C, Sato T, Kawada T, Sugimachi M, Sunagawa K (2004) Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation 109:120–124. doi:10.1161/01.CIR.0000105721.71640.DA

    Article  PubMed  Google Scholar 

  38. Ma H, Zhang HF, Yu L, Zhang QJ, Li J, Huo JH, Li X, Guo WY, Wang HC, Gao F (2006) Vasculoprotective effect of insulin in the ischemic/reperfused canine heart: role of Akt-stimulated NO production. Cardiovasc Res 69:57–65. doi:10.1016/j.cardiores.2005.08.019

    Article  PubMed  CAS  Google Scholar 

  39. Mendelsohn ME, Karas RH (2005) Molecular and cellular basis of cardiovascular gender differences. Science 308:1583–1587. doi:10.1126/science.1112062

    Article  PubMed  CAS  Google Scholar 

  40. Mioni C, Bazzani C, Giuliani D, Altavilla D, Leone S, Ferrari A, Minutoli L, Bitto A, Marini H, Zaffe D, Botticelli AR, Iannone A, Tomasi A, Bigiani A, Bertolini A, Squadrito F, Guarini S (2005) Activation of an efferent cholinergic pathway produces strong protection against myocardial ischemia/reperfusion injury in rats. Crit Care Med 33:2621–2628. doi:10.1097/01.CCM.0000186762.05301.13

    Article  PubMed  CAS  Google Scholar 

  41. Payrits T, Ernst A, Ladits E, Pokorny H, Viragos I, Langle F (2011) Vagal stimulation—a new possibility for conservative treatment of peripheral arterial occlusion disease. Zentralbl Chir 136:431–435. doi:10.1055/s-0031-1283739

    Article  PubMed  CAS  Google Scholar 

  42. Sadis C, Teske G, Stokman G, Kubjak C, Claessen N, Moore F, Loi P, Diallo B, Barvais L, Goldman M, Florquin S, Le Moine A (2007) Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway. PLoS One 2:e469. doi:10.1371/journal.pone.0000469

    Article  PubMed  Google Scholar 

  43. Saleh TM, Connell BJ (2000) 17beta-estradiol modulates baroreflex sensitivity and autonomic tone of female rats. J Auton Nerv Syst 80:148–161. doi:10.1016/S0165-1838(00)00087-4

    Article  PubMed  CAS  Google Scholar 

  44. Shantsila E, Wrigley BJ, Blann AD, Gill PS, Lip GY (2012) A contemporary view on endothelial function in heart failure. Eur J Heart Fail 14:873–881. doi:10.1093/eurjhf/hfs066

    Article  PubMed  CAS  Google Scholar 

  45. Sun L, Lu J, Yu XJ, Li DL, Xu XL, Wang B, Ren KY, Liu JK, Zang WJ (2011) Adenine sulfate improves cardiac function and the cardiac cholinergic system after myocardial infarction in rats. J Pharmacol Sci 115:205–213. doi:10.1254/jphs.10231FP

    Article  PubMed  CAS  Google Scholar 

  46. Taggart P, Critchley H, Lambiase PD (2011) Heart-brain interactions in cardiac arrhythmia. Heart 97:698–708. doi:10.1136/hrt.2010.209304

    Article  PubMed  CAS  Google Scholar 

  47. Tiedt N, Religa A (1979) Vagal control of coronary blood flow in dogs. Basic Res Cardiol 74:266–276. doi:10.1007/BF01907744

    Article  PubMed  CAS  Google Scholar 

  48. Tracey KJ (2002) The inflammatory reflex. Nature 420:853–859. doi:10.1038/nature01321

    Article  PubMed  CAS  Google Scholar 

  49. Tracey KJ (2007) Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 117:289–296. doi:10.1172/JCI30555

    Article  PubMed  CAS  Google Scholar 

  50. Uemura K, Li M, Tsutsumi T, Yamazaki T, Kawada T, Kamiya A, Inagaki M, Sunagawa K, Sugimachi M (2007) Efferent vagal nerve stimulation induces tissue inhibitor of metalloproteinase-1 in myocardial ischemia-reperfusion injury in rabbit. Am J Physiol Heart Circ Physiol 293:H2254–H2261. doi:10.1152/ajpheart.00490.2007

    Article  PubMed  CAS  Google Scholar 

  51. Ulloa L (2005) The vagus nerve and the nicotinic anti-inflammatory pathway. Nat Rev Drug Discov 4:673–684. doi:10.1038/nrd1797

    Article  PubMed  CAS  Google Scholar 

  52. Ulphani JS, Cain JH, Inderyas F, Gordon D, Gikas PV, Shade G, Mayor D, Arora R, Kadish AH, Goldberger JJ (2010) Quantitative analysis of parasympathetic innervation of the porcine heart. Heart Rhythm 7:1113–1119. doi:10.1016/j.hrthm.2010.03.043

    Article  PubMed  Google Scholar 

  53. van Westerloo DJ, Giebelen IA, Florquin S, Bruno MJ, Larosa GJ, Ulloa L, Tracey KJ, van der Poll T (2006) The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. Gastroenterology 130:1822–1830. doi:10.1053/j.gastro.2006.02.022

    Article  PubMed  Google Scholar 

  54. Vinten-Johansen J (2004) Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury. Cardiovasc Res 61:481–497. doi:10.1016/j.cardiores.2003.10.011

    Article  PubMed  CAS  Google Scholar 

  55. Virdis A, Colucci R, Fornai M, Blandizzi C, Duranti E, Pinto S, Bernardini N, Segnani C, Antonioli L, Taddei S, Salvetti A, Del Tacca M (2005) Cyclooxygenase-2 inhibition improves vascular endothelial dysfunction in a rat model of endotoxic shock: role of inducible nitric-oxide synthase and oxidative stress. J Pharmacol Exp Ther 312:945–953. doi:10.1124/jpet.104.077644

    Article  PubMed  CAS  Google Scholar 

  56. Wada M, Kira M, Nakaji Y, Ikeda R, Kuroda N, Nakashima K (2012) Development of a novel method for monitoring the antioxidative effect of ascorbic acid in rat blood. Food Chem 134:546–552. doi:10.1016/j.foodchem.2012.02.117

    Article  CAS  Google Scholar 

  57. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384–388. doi:10.1038/nature01339

    Article  PubMed  CAS  Google Scholar 

  58. Wang Q, Tang XN, Yenari MA (2007) The inflammatory response in stroke. J Neuroimmunol 184:53–68. doi:10.1016/j.jneuroim.2006.11.014

    Article  PubMed  CAS  Google Scholar 

  59. Wang WZ, Fang XH, Stepheson LL, Khiabani KT, Zamboni WA (2004) NOS upregulation attenuates vascular endothelial dysfunction in the late phase of ischemic preconditioning in skeletal muscle. J Orthop Res 22:578–585. doi:10.1016/j.orthres.2003.10.004

    Article  PubMed  CAS  Google Scholar 

  60. Xiong J, Yuan YJ, Xue FS, Wang Q, Cheng Y, Li RP, Liao X, Liu JH (2012) Postconditioning with α7nAChR agonist attenuates systemic inflammatory response to myocardial ischemia–reperfusion injury in rats. Inflammation 35:1357–1364. doi:10.1007/s10753-012-9449-2

    Article  PubMed  CAS  Google Scholar 

  61. Yeboah MM, Xue X, Duan B, Ochani M, Tracey KJ, Susin M, Metz CN (2008) Cholinergic agonists attenuate renal ischemia-reperfusion injury in rats. Kidney Int 74:62–69. doi:10.1038/ki.2008.94

    Article  PubMed  CAS  Google Scholar 

  62. Zhang C, Wu J, Xu X, Potter BJ, Gao X (2010) Direct relationship between levels of TNF-alpha expression and endothelial dysfunction in reperfusion injury. Basic Res Cardiol 105:453–464. doi:10.1007/s00395-010-0083-6

    Article  PubMed  CAS  Google Scholar 

  63. Zhang C, Xu X, Potter BJ, Wang W, Kuo L, Michael L, Bagby GJ, Chilian WM (2006) TNF-alpha contributes to endothelial dysfunction in ischemia/reperfusion injury. Arterioscler Thromb Vasc Biol 26:475–480. doi:10.1161/01.ATV.0000201932.32678.7e

    Article  PubMed  CAS  Google Scholar 

  64. Zhao M, He X, Wier WG, Zhang HL, Zhao M, Yu XJ, Zang WJ (2012) Endothelial dysfunction in rat mesenteric artery after regional cardiac ischaemia-reperfusion. Exp Physiol 97:70–79. doi:10.1113/expphysiol.2011.059360

    Article  PubMed  CAS  Google Scholar 

  65. Zhao M, He X, Zhao M, Bi XY, Zhang HL, Yu XJ, Liu JJ, Li DL, Ma X, Zang WJ (2012) Low-dose celecoxib improves coronary function after acute myocardial ischaemia in rabbits. Clin Exp Pharmacol Physiol 39:233–240. doi:10.1111/j.1440-1681.2011.05664.x

    Article  PubMed  CAS  Google Scholar 

  66. Zuanetti G, De Ferrari GM, Priori SG, Schwartz PJ (1987) Protective effect of vagal stimulation on reperfusion arrhythmias in cats. Circ Res 61:429–435. doi:10.1161/01.RES.61.3.429

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Prof. John Y-J. Shyy (Ohio State University) for the discussion about the experiment design. We also appreciate the technical support and materials from the electron microscope Center of Xi’an Jiaotong University. This work is supported by Major International (Regional) Joint Research Project of National Natural Science Foundation of China (No. 81120108002), National Natural Science Foundation of China (Key program, No. 30930105; General program, No. 30873058), CMB Distinguished Professorships Award (No. F510000/G16916404) and Natural Science Foundation of Shaanxi Province (No. 2012JZ4001).

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  1. Department of Pharmacology, College of Medicine, Xi’an Jiaotong University, No. 76 Yanta West Road, P.O. Box 77#, Xi’an, 710061, People’s Republic of China

    Ming Zhao, Xi He, Xue-Yuan Bi, Xiao-Jiang Yu & Wei-Jin Zang

  2. Departments of Physiology and Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    W. Gil Wier

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  1. Ming Zhao
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Correspondence to Wei-Jin Zang.

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M. Zhao and X. He contributed equally to this work.

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Zhao, M., He, X., Bi, XY. et al. Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion. Basic Res Cardiol 108, 345 (2013). https://doi.org/10.1007/s00395-013-0345-1

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