title: Peripheral versus central muscarinic effects on blood pressure, cardiac contractility, heart rate, and body temperature in the rat monitored by radiotelemetry.
abstract: 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.affiliation: Norfolk State University, Department of Biological Sciences, Virginia 23504-8060, USA. smith.edward@epamail.epa.gov
authors.forename: E C
authors.initials: EC
authors.lastname: Smith
authors.forename: B
authors.initials: B
authors.lastname: Padnos
authors.forename: C J
authors.initials: CJ
authors.lastname: Cordon
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D019832:N-Methylscopolamine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D013686:Telemetry
chemical_list: D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010095:Oxotremorine; D019832:N-Methylscopolamine