title: Cardiovascular collapse through non-cholinergic mechanism after intravenous injection of N-methylcarbamate insecticide in rabbits.
abstract: This study was undertaken to investigate whether cholinesterase (ChE) inhibitor exerts cardiovascular collapse through non-cholinergic mechanism in halothane-anesthetized rabbits. Physostigmine and N-methylcarbamate insecticides (BPMC = 2-sec-butylphenyl methylcarbamate and PHC = propoxur = 2-isopropoxyphenyl methylcarbamate) were employed as ChE inhibitors. Intravenous injection of physostigmine produced a dose-related pressor response a few minutes after the injection. In contrast, the injection of BPMC elicited a dose-related depressor response during the injection. PHC produced a slight depressor response during the injection followed by a dose-dependent pressor response. Norepinephrine (NE)-induced pressor response was inhibited by the ChE inhibitors with the same order and magnitude as the depressor response. ECG of physostigmine or PHC was characterized by an increase in QRS voltage and a sinus bradycardia, and that of BPMC by a decrease in QRS voltage. Atropine pretreatment inhibited the pressor response, the increase in QRS voltage and the sinus bradycardia, but not the depressor response and the decrease in QRS voltage. From these observations, it is suggested that the pressor response is ascribed to the cholinergic mechanism (acetylcholine accumulation through ChE inhibition), but the depressor response may result from a non-cholinergic mechanism. It is also suggested that the difference in the cardiovascular response is determined by a balance between cholinergic and non-cholinergic activity of each ChE inhibitor.
authors.affiliation: Institute of Environmental Toxicology, Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Futagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kakinuma
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002219:Carbamates / Q000008:administration & dosage / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004562:Electrocardiography; D006973:Hypertension / Q000139:chemically induced; D007275:Injections, Intravenous; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage; D010830:Physostigmine / Q000494:pharmacology; D001074:Propoxur / Q000494:pharmacology; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012770:Shock, Cardiogenic / Q000139:chemically induced*
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D011950:Receptors, Cholinergic; C019276:BPMC; C020401:N-methylcarbamate; D010830:Physostigmine; D001074:Propoxur; D009638:Norepinephrine