The effects of chlorpyrifos on blood pressure and temperature regulation in spontaneously hypertensive rats.
Using radiotelemetry to monitor blood pressure and core temperature, studies in our laboratory have shown that a prolonged hypertensive response is elicited in rats exposed to chlorpyrifos, an organophosphate-based insecticide. Chlorpyrifos inhibits acetylcholinesterase activity, resulting in central and peripheral stimulation of central cholinergic pathways involved in blood pressure regulation. The spontaneously hypertensive rat has been shown to be more sensitive to central cholinergic stimulation. Therefore, we hypothesized that these rats would be more susceptible and sustain a greater hypertensive response when exposed to chlorpyrifos. Heart rate, cardiac contractility, core temperature, and blood pressure were monitored by radiotelemetry in SHRs and their Wistar Kyoto (WKY) normotensive controls following exposure to chlorpyrifos (10 mg/kg or 25 mg/kg, orally). Baseline blood pressure of SHRs was approximately 35 mmHg above that of WKYs prior to dosing. SHRs exhibited a greater and more sustained elevation in diastolic, mean and systolic blood pressure following exposure to 25 mg/kg of chlorpyrifos. The rise in blood pressure lasted for approximately 56 hours in SHRs compared to approximately 32 hours in WKYs. Chlorpyrifos also led to a prolonged elevation in daytime heart rate in both strains. There was a transient elevation in cardiac contractility in both strains lasting approximately 7 hr after exposure to chlorpyrifos. The hypothermic response to chlorpyrifos was similar in magnitude and duration for both strains. Plasma cholinesterase activity measured 4 hr after exposure to 25 mg/kg chlorpyrifos was inhibited to approximately 40% of control levels in both strains. Using the SHR strain as a model to study susceptible populations, the data suggest that individuals with a genetic predisposition to hypertension may be more susceptible from exposure to organophosphate-based insecticide, as manifested by an exacerbated hypertensive response.
Smith
Edward G
EG
Livingstone College, Department of Biological Sciences, 701 West Monroe Street, Salisbury, North Carolina 28144, USA.
Gordon
Christopher J
CJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology*; D013045:Species Specificity; D013686:Telemetry
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D002802:Cholinesterases; D004390:Chlorpyrifos