title: Differential acetylcholine release mechanisms in the ischemic and non-ischemic myocardium.
abstract: To understand better the pathophysiological roles of the vagal efferent system in ischemic heart diseases, we examined endogenous acetylcholine (ACh) release in the myocardium in vivo. Acute myocardial ischemia was induced in anesthetized cats by a 60-min occlusion of the left anterior descending coronary artery (LAD). We implanted dialysis probes in the left ventricular free wall and measured the dialysate ACh concentration using liquid chromatography. In the ischemic region, the ACh level increased from 0.68+/-0.12 to 12.3+/-3.3 n M (mean+/-S.E., P<0.01) by LAD occlusion. Bilateral vagotomy did not inhibit ischemia-induced ACh release (20.3+/-6.4 n M). In vagotomized animals, inhibition of the N-type Ca(2+)channel by intravenous administration of omega-conotoxin GVIA (10microg/kg) also failed to suppress ACh release (15.9+/-2.0 n M). However, the inhibition of intracellular Ca(2+)mobilization by local administration of 3,4,5-trimethoxybenzoic acid 8-(dietyl amino)-octyl ester (1 m M) suppressed ACh release (4.4+/-0.8 n M, P<0.05 compared with no pharmacological intervention). In the non-ischemic region, the ACh level increased from 1.9+/-0.4 to 6. 0+/-1.0 n M (P<0.05) by LAD occlusion, which was completely abolished by vagotomy. We concluded that ACh release in the ischemic region was mainly attributed to a local release mechanism, whereas that in the non-ischemic region depended on the presence of intact vagal activity. The local release mechanism would depend on intracellular Ca(2+)mobilization but not on N-type Ca(2+)channel opening.
authors.affiliation: Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawada
authors.forename: T
authors.initials: T
authors.lastname: Yamazaki
authors.forename: T
authors.initials: T
authors.lastname: Akiyama
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Shishido
authors.forename: M
authors.initials: M
authors.lastname: Inagaki
authors.forename: H
authors.initials: H
authors.lastname: Takaki
authors.forename: M
authors.initials: M
authors.lastname: Sugimachi
authors.forename: K
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000378:metabolism; D002415:Cats; D004195:Disease Models, Animal; D005707:Gallic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D020866:omega-Conotoxin GVIA / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D020866:omega-Conotoxin GVIA; D000109:Acetylcholine; D009638:Norepinephrine