title: Role of acetylcholine in pyridostigmine-induced myocardial injury: possible involvement of parasympathetic nervous system in the genesis of cardiomyopathy.
abstract: Although acetylcholine is known to be involved in the genesis of skeletal muscle disturbance, its effect on cardiac muscle has been scarcely studied. In the present paper, using pyridostigmine, a cholinesterase inhibitor, the possible role of acetylcholine in the genesis of cardiomyopathy was investigated. In a mortality study, it was shown that pyridostigmine (100 mg/kg) caused death of 9/10 rats within 8 h, and that the lethality of such a dose could be significantly diminished by the subsequent administration of a total dose of 4 mg/kg atropine. In all other experiments, rats were divided into three groups; the control, untreated group; the pyridostigmine + atropine group in which atropine (2 mg/kg) was administered 5 min after pyridostigmine (60 mg/kg) administration; and the pyridostigmine group in which pyridostigmine (60 mg/kg) was administered orally. Rats were killed 3 h after pyridostigmine administration, and hearts were isolated. Heart mitochondrial electron transport activity (NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase) were measured enzymatically, and mitochondrial respiratory rates and control indices were measured polarographically. Structural changes in cardiac muscles of each group were observed by electron microscopy of cardiac sections. Acetylcholine levels of left ventricle were measured by high performance liquid chromatography. Activities of NADH-cytochrome c reductase and succinate-cytochrome c reductase were not affected by pyridostigmine administration; however, cytochrome c oxidase activity was significantly reduced in the pyridostigmine group. Atropine markedly lessened this reduction in activity. A protective effect of atropine was also observed morphologically. A protective effect of atropine was also observed morphologically. In the pyridostigmine group and the pyridostigmine + atropine group, left ventricular acetylcholine levels were increased significantly compared with the control.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Hanaki
authors.forename: A
authors.initials: A
authors.lastname: Fukushima
authors.forename: N
authors.initials: N
authors.lastname: Akiyama
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Ozawa
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D006321:Heart / Q000294:innervation; D006331:Heart Diseases / Q000139:chemically induced*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011729:Pyridostigmine Bromide / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D011729:Pyridostigmine Bromide; D000109:Acetylcholine