skip to main content

Title: Acute effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate, on cardiovascular parameters in anaesthetized, artificially ventilated rats

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 (0.8 mg/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 (1 mg/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. - Highlights: • A sarin-like agent BIMP markedly increasedmore » blood pressure in anaesthetized rats. • Muscarinic receptor blockade enhanced the BIMP-induced increase in blood pressure. • Ganglionic nicotinic receptor blockade attenuated the BIMP-induced response. • Blockade of α- as well as β-receptors attenuated the BIMP-induced response.« less
Authors:
 [1] ;  [1] ;  [2] ;  [3] ; ; ;  [2] ;  [4] ;  [5] ;  [2]
  1. Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan)
  2. Department of Forensic Medicine, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan)
  3. Department of Forensic Medical Science, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan)
  4. Department of Nursing, Faculty of Health Sciences, Hiroshima Cosmopolitan University, Hiroshima (Japan)
  5. Department of Cardiovascular Physiology and Medicine, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan)
Publication Date:
OSTI Identifier:
22285395
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 272; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ATROPINE; BLOOD PRESSURE; HEART; ORGANIC PHOSPHORUS COMPOUNDS; RATS; RECEPTORS; TOXICITY