Document Detail


Peripheral versus central muscarinic effects on blood pressure, cardiac contractility, heart rate, and body temperature in the rat monitored by radiotelemetry.
MedLine Citation:
PMID:  11484908     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our laboratory has found that the organophosphate pesticide chlorpyrifos elicits an elevation in blood pressure that persists for approximately 24 hr after exposure. Since organophosphate pesticides inhibit acetylcholinesterase activity and cause cholinergic stimulation in the central nervous system and peripheral tissues, we suspect that the hypertensive response from chlorpyrifos is elicited by activation of pressor areas in the brain stem, specifically muscarinic receptors which are known to mediate hypertensive responses. Oxotremorine, a muscarinic agonist, should elicit a blood pressure response similar to organophosphate pesticides. This study used radiotelemetry to assess the effects of oxotremorine on blood pressure, heart rate, core temperature, QA interval (a measure of cardiac contractility), and motor activity in the male, Long-Evans rat. Subcutaneous co-administration of 0.2 mg/kg oxotremorine with 1.0 mg/kg methyl scopolamine (i.e., to block oxotremorine's peripheral effects) caused a marked elevation in blood pressure that developed concomitantly with a 2 degrees decrease in core temperature, 60 beats/min. increase in heart rate, increase in cardiac contractility but no change in motor activity. Overall, blood pressure increased by 19 mmHg from baseline and the response persisted for approximately 12 hr after injection. Methyl scopolamine alone increased heart rate but had no effect on blood pressure, core temperature, and motor activity. Oxotremorine injected without methyl scopolamine led to a relatively minor increase in blood pressure and hypothermia. Overall, central muscarinic stimulation with oxotremorine and methyl scopolamine leads to a vigorous hypertensive response that is associated with increased cardiac contractility, suggesting an increase in cardiac output. Combined central and peripheral cholinergic stimulation following oxotremorine without methyl scopolamine, as would also occur with exposure to chlorpyrifos and other organophosphate pesticides, did not elicit as much of a hypertensive response. This would suggest pathways other than those controlled directly with muscarinic receptors are operative in the development of chlorpyrifos-induced hypertension.
Authors:
E C Smith; B Padnos; C J Cordon
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmacology & toxicology     Volume:  89     ISSN:  0901-9928     ISO Abbreviation:  Pharmacol. Toxicol.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-08-03     Completed Date:  2001-12-18     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8702180     Medline TA:  Pharmacol Toxicol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  35-42     Citation Subset:  IM    
Affiliation:
Norfolk State University, Department of Biological Sciences, Virginia 23504-8060, USA. smith.edward@epamail.epa.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects*
Body Temperature / drug effects
Drug Interactions
Heart Rate / drug effects*
Male
Motor Activity / drug effects
Muscarinic Agonists / pharmacology*
Muscarinic Antagonists / pharmacology
Myocardial Contraction / drug effects*
N-Methylscopolamine / pharmacology
Oxotremorine / pharmacology*
Parasympatholytics / pharmacology
Rats
Rats, Long-Evans
Telemetry
Chemical
Reg. No./Substance:
0/Muscarinic Agonists; 0/Muscarinic Antagonists; 0/Parasympatholytics; 13265-10-6/N-Methylscopolamine; 70-22-4/Oxotremorine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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