title: Nitric oxide is involved in acetylcholinesterase inhibitor-induced myopathy in rats.
abstract: Excess activation of muscle nicotinic acetylcholine receptors due to genetic mutations, as seen in slow channel congenital myasthenic syndrome, or acetylcholinesterase (AChE) inhibition results in muscle cell degeneration. Our recent work showed that nitric oxide synthase (NOS) inhibitors prevent nicotine-induced muscle cell death in culture. In the present study, we examined the effects of NOS inhibition on nicotinic receptor-mediated myopathy in vivo. Rats injected with the AChE inhibitor paraoxon demonstrate a 90-fold increase in the number of dying muscle cells compared with control as evidenced histologically by centralized nuclei and the presence of degenerating profiles. Coadministration of the nonspecific NOS inhibitor nitro-L-arginine methyl ester or the neuronal NOS-specific inhibitor 7-nitroindazole dramatically reduced the presence of such degenerating profiles to approximately 20% of that seen with paraoxon alone. These results show that inhibition of NOS, as well as neuronal NOS, significantly reduces AChE inhibitor-induced muscle cell degeneration, suggesting that increased nitric oxide production mediates such myopathy.
authors.affiliation: The Parkinson's Institute, Sunnyvale, California, USA.
authors.forename: G
authors.initials: G
authors.lastname: Jeyarasasingam
authors.forename: M
authors.initials: M
authors.lastname: Yeluashvili
authors.forename: M
authors.initials: M
authors.lastname: Quik
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009132:Muscles / Q000201:enzymology; D009135:Muscular Diseases / Q000139:chemically induced*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D010261:Paraoxon / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010261:Paraoxon; D019331:NG-Nitroarginine Methyl Ester