title: Efferent vagal nerve stimulation induces tissue inhibitor of metalloproteinase-1 in myocardial ischemia-reperfusion injury in rabbit.
abstract: Vagal nerve stimulation has been suggested to ameliorate left ventricular (LV) remodeling in heart failure. However, it is not known whether and to what degree vagal nerve stimulation affects matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) in myocardium, which are known to play crucial roles in LV remodeling. We therefore investigated the effects of electrical stimulation of efferent vagal nerve on myocardial expression and activation of MMPs and TIMPs in a rabbit model of myocardial ischemia-reperfusion (I/R) injury. Anesthetized rabbits were subjected to 60 min of left coronary artery occlusion and 180 min of reperfusion with (I/R-VS, n = 8) or without vagal nerve stimulation (I/R, n = 7). Rabbits not subjected to coronary occlusion with (VS, n = 7) or without vagal stimulation (sham, n = 7) were used as controls. Total MMP-9 protein increased significantly after left coronary artery occlusion in I/R-VS and I/R to a similar degree compared with VS and sham values. Endogenous active MMP-9 protein level was significantly lower in I/R-VS compared with I/R. TIMP-1 mRNA expression was significantly increased in I/R-VS compared with the I/R, VS, and sham groups. TIMP-1 protein was significantly increased in I/R-VS and VS compared with the I/R and sham groups. Cardiac microdialysis technique demonstrated that topical perfusion of acetylcholine increased dialysate TIMP-1 protein level, which was suppressed by coperfusion of atropine. Immunohistochemistry demonstrated a strong expression of TIMP-1 protein in cardiomyocytes around the dialysis probe used to perfuse acetylcholine. In conclusion, in a rabbit model of myocardial I/R injury, vagal nerve stimulation induced TIMP-1 expression in cardiomyocytes and reduced active MMP-9.
authors: Dept. of Cardiovascular Dynamics, National Cardiovascular Center Research Inst., 5-7-1 Fujishirodai, Suita 565-8565, Japan. kuemura@ri.ncvc.go.jp
authors: Kazunori
authors: K
authors: Uemura
authors: Meihua
authors: M
authors: Li
authors: Takaki
authors: T
authors: Tsutsumi
authors: Toji
authors: T
authors: Yamazaki
authors: Toru
authors: T
authors: Kawada
authors: Atsunori
authors: A
authors: Kamiya
authors: Masashi
authors: M
authors: Inagaki
authors: Kenji
authors: K
authors: Sunagawa
authors: Masaru
authors: M
authors: Sugimachi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure; D018678:Cholinergic Agents / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004525:Efferent Pathways / Q000187:drug effects / Q000503:physiopathology; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006339:Heart Rate; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D017551:Microdialysis; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012107:Research Design; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
chemical_list: D018678:Cholinergic Agents; D018680:Cholinergic Antagonists; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D001285:Atropine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000109:Acetylcholine