Role of Acetylcholine in Pyridostigmine-induced Myocardial Injury: Possible Involvement of Parasympathetic Nervous System in the Genesis of Cardiomyopathy

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 1989 Jan 1

PMID 2730338

Authors

T Kato

S Sugiyama

Y Hanaki

A Fukushima

N Akiyama

T Ito

T Ozawa

Affiliations

Soon will be listed here.

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)

References

Tsuboi H, Ohno O, Ogawa K, Ito T, Hashimoto H, Okumura K . Acetylcholine and norepinephrine concentrations in the heart of spontaneously hypertensive rats: a parasympathetic role in hypertension. J Hypertens. 1987; 5(3):323-30. DOI: 10.1097/00004872-198706000-00010. View

Stanley R, Conatser J, Dettbarn W . Acetylcholine, choline acetyltransferase and cholinesterases in the rat heart. Biochem Pharmacol. 1978; 27(20):2409-11. DOI: 10.1016/0006-2952(78)90352-0. View

Sugiyama S, Takamura T, Ajioka M, NAGAI S, Ozawa T . Mechanism of myocardial injury in dogs with hypokalaemia. Cardiovasc Res. 1988; 22(4):249-54. DOI: 10.1093/cvr/22.4.249. View

Ogawa Y, Kondo T, Sugiyama S, Ogawa K, Satake T, Ozawa T . Role of phospholipase in the genesis of doxorubicin-induced cardiomyopathy in rats. Cancer Res. 1987; 47(5):1239-43. View

Kondo T, Ogawa Y, Sugiyama S, Ito T, Satake T, Ozawa T . Mechanism of isoproterenol induced myocardial damage. Cardiovasc Res. 1987; 21(4):248-54. DOI: 10.1093/cvr/21.4.248. View

Salpeter M, Kasprzak H, Feng H, Fertuck H . Endplates after esterase inactivation in vivo: correlation between esterase concentration, functional response and fine structure. J Neurocytol. 1979; 8(1):95-115. DOI: 10.1007/BF01206461. View

Hieda N, Toki Y, Sugiyama S, Ito T, Satake T, Ozawa T . Prostaglandin I2 analogue and propranolol prevent ischaemia induced mitochondrial dysfunction through the stabilisation of lysosomal membranes. Cardiovasc Res. 1988; 22(3):219-25. DOI: 10.1093/cvr/22.3.219. View

Potter P, Meek J, Neff N . Acetylcholine and choline in neuronal tissue measured by HPLC with electrochemical detection. J Neurochem. 1983; 41(1):188-94. DOI: 10.1111/j.1471-4159.1983.tb13668.x. View

Kiss Z, Fazekas T . Arrhythmias in organophosphate poisonings. Acta Cardiol. 1979; 34(5):323-30. View

10.

HATEFI Y, Jurtshuk P, HAAVIK A . Studies on the electron transport system. 32. Respiratory control in beef heart mitochondria. Arch Biochem Biophys. 1961; 94:148-55. DOI: 10.1016/0003-9861(61)90022-4. View

11.

Marin-Neto J, Maciel B, Gallo Junior L, Junqueira Junior L, Amorim D . Effect of parasympathetic impairment on the haemodynamic response to handgrip in Chagas's heart disease. Br Heart J. 1986; 55(2):204-10. PMC: 1232119. DOI: 10.1136/hrt.55.2.204. View

12.

Rona G, Chappel C, Balazs T, GAUDRY R . An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol. 1959; 67(4):443-55. View

13.

Horio Y, Yasue H, Rokutanda M, Nakamura N, Ogawa H, Takaoka K . Effects of intracoronary injection of acetylcholine on coronary arterial diameter. Am J Cardiol. 1986; 57(11):984-9. DOI: 10.1016/0002-9149(86)90743-5. View

14.

Kawabuchi M, Osame M, Watanabe S, Igata A, Kanaseki T . Myopathic changes at the end-plate region induced by neostigmine methylsulfate. Experientia. 1976; 32(5):632-5. DOI: 10.1007/BF01990200. View

15.

MANNING G, Hall G, Banting F . VAGUS STIMULATION AND THE PRODUCTION OF MYOCARDIAL DAMAGE. Can Med Assoc J. 2010; 37(4):314-8. PMC: 536140. View

16.

Dettbarn W . Pesticide induced muscle necrosis: mechanisms and prevention. Fundam Appl Toxicol. 1984; 4(2 Pt 2):S18-26. DOI: 10.1016/0272-0590(84)90134-9. View

17.

Gebbers J, Lotscher M, Kobel W, Portmann R, Laissue J . Acute toxicity of pyridostigmine in rats: histological findings. Arch Toxicol. 1986; 58(4):271-5. DOI: 10.1007/BF00297119. View

18.

Katada T, Northup J, Bokoch G, Ui M, GILMAN A . The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Subunit dissociation and guanine nucleotide-dependent hormonal inhibition. J Biol Chem. 1984; 259(6):3578-85. View

19.

Bossaller C, HABIB G, Yamamoto H, Williams C, Wells S, Henry P . Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest. 1987; 79(1):170-4. PMC: 424014. DOI: 10.1172/JCI112779. View

20.

Oliveira J . A natural human model of intrinsic heart nervous system denervation: Chagas' cardiopathy. Am Heart J. 1985; 110(5):1092-8. DOI: 10.1016/0002-8703(85)90222-4. View