title: Acute effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate, on cardiovascular parameters in anaesthetized, artificially ventilated rats.
abstract: The organophosphorus compound sarin irreversibly inhibits acetylcholinesterase. We examined the acute cardiovascular effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate (BIMP), in anaesthetized, artificially ventilated rats. Intravenous administration of BIMP (0.8mg/kg; the LD50 value) induced a long-lasting increase in blood pressure and tended to increase heart rate. In rats pretreated with the non-selective muscarinic-receptor antagonist atropine, BIMP significantly increased both heart rate and blood pressure. In atropine-treated rats, hexamethonium (antagonist of ganglionic nicotinic receptors) greatly attenuated the BIMP-induced increase in blood pressure without changing the BIMP-induced increase in heart rate. In rats treated with atropine plus hexamethonium, intravenous phentolamine (non-selective α-adrenergic receptor antagonist) plus propranolol (non-selective β-adrenergic receptor antagonist) completely blocked the BIMP-induced increases in blood pressure and heart rate. In atropine-treated rats, the reversible acetylcholinesterase inhibitor neostigmine (1mg/kg) induced a transient increase in blood pressure, but had no effect on heart rate. These results suggest that in anaesthetized rats, BIMP induces powerful stimulation of sympathetic as well as parasympathetic nerves and thereby modulates heart rate and blood pressure. They may also indicate that an action independent of acetylcholinesterase inhibition contributes to the acute cardiovascular responses induced by BIMP.
authors.affiliation: Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Takeo
authors.initials: T
authors.lastname: Itoh
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiraishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Maeno
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Arima
authors.forename: Aiko
authors.initials: A
authors.lastname: Torikoshi
authors.forename: Akira
authors.initials: A
authors.lastname: Namera
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Makita
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Masataka
authors.initials: M
authors.lastname: Nagao
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004164:Diphosphonates / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects; D012121:Respiration, Artificial; D012524:Sarin / Q000031:analogs & derivatives* / Q000633:toxicity*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002619:Chemical Warfare Agents; D004164:Diphosphonates; D018727:Muscarinic Antagonists; D011978:Receptors, Nicotinic; C109992:bis(isopropyl methyl)phosphonate; D001285:Atropine; D012524:Sarin
keywords: Adrenergic receptor antagonists; Cardiovascular toxicity; Irreversible acetylcholinesterase inhibitor; Organophosphates; Sarin