Intermittent Exposure to Chlorpyrifos Differentially Impacts Neuroreflex Control of Cardiorespiratory Function in Rats

Cardiovasc Toxicol. 2019 Dec;19(6):548-564. doi: 10.1007/s12012-019-09528-7.

Abstract

Previous studies showed that chlorpyrifos (CPF) acute exposure impaired cardiorespiratory reflexes. Evidence also indicates that continuous exposure to organophosphorus compounds impairs cardiovascular function. However, the effect of intermittent exposure to CPF, as may be experienced in the real world, on tonic and reflex cardiorespiratory function remains unexplored. Wistar rats were injected with saline or CPF for 4 weeks (3 times/week) or 12 weeks (once/week) at the doses of 7 mg/kg and 10 mg/kg. After exposure, blood pressure (BP), heart rate (HR), respiratory rate (fR), tidal volume (VT), and minute volume (VE) were recorded. Systolic BP and pulse interval (PI) variability, HR spectrum, spontaneous baroreflex and chemoreflex function were also evaluated. Plasma butyrylcholinesterase and brainstem acetylcholinesterase activities were quantified. Enzymatic activity of the CPF animals was reduced after both treatment periods. Baseline BP, HR, and fR, as well as systolic BP and PI variability indices, did not change, after CPF treatment. VT and VE were elevated in CPF animals. CPF exposure increased the very low-frequency component of the HR spectrum. Baroreflex gain was reduced after CPF 4-week exposure. Chemoreflex bradycardia was reduced in the CPF-treated rats. These data show that intermittent exposure to CPF impairs cardiorespiratory function in rats. These results may have important clinical implications for workers seasonally exposed to these compounds.

Keywords: Acetylcholinesterase; Baroreflex; Butyrylcholinesterase; Cardiovascular variability; Chemoreflex; Chlorpyrifos.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Baroreflex / drug effects*
  • Blood Pressure / drug effects
  • Brain Stem / drug effects*
  • Brain Stem / enzymology
  • Brain Stem / physiopathology
  • Butyrylcholinesterase / blood
  • Cardiotoxicity
  • Chemoreceptor Cells / drug effects
  • Chemoreceptor Cells / metabolism
  • Chlorpyrifos / toxicity*
  • Cholinesterase Inhibitors / toxicity*
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / metabolism
  • Heart / innervation*
  • Heart Rate / drug effects
  • Insecticides / toxicity*
  • Lung / innervation*
  • Male
  • Rats, Wistar
  • Respiratory Rate / drug effects
  • Tidal Volume / drug effects
  • Time Factors

Substances

  • Cholinesterase Inhibitors
  • GPI-Linked Proteins
  • Insecticides
  • Acetylcholinesterase
  • Ache protein, rat
  • Butyrylcholinesterase
  • Chlorpyrifos