Effect of cyclic phenyl saligenin phosphate and paraoxon treatment on vascular response to adrenergic and cholinergic agents in hens

J Toxicol Environ Health. 1995 Feb;44(2):167-87. doi: 10.1080/15287399509531953.

Abstract

The response of peripheral blood vessels to adrenergic and cholinergic agonists was examined 1, 3, 7, and 21 d after hens were treated with a single intramuscular injection of 2.5 mg/kg cyclic phenyl saligenin phosphate (PSP) or 0.10 mg/kg paraoxon (PXN). These two organophosphates (OPs) cause different clinical effects in exposed animals, as PSP causes organophosphate-induced delayed neuropathy (OPIDN) and PXN causes acute poisoning through inhibition of acetylcholinesterase. For these studies, the ischiadic artery was cannulated both prograde and retrograde and the blood was shunted through a pump to maintain a constant flow. Alterations in pressure measured at the pump outflow were used to indicate changes in limb vascular resistance. Dose-response curves were generated for the response to intravenous administration of acetylcholine (ACh), phenylephrine (PE), or salbutamol (SAL) (10(-8) to 10(-4) mol/kg). Acetylcholine at 10(-8) to 10(-7) mol/kg caused an increase in vascular resistance, whereas concentrations of 10(-5) to 10(-4) mol/kg caused a decrease in vascular resistance in hens given PSP 1 and 3 d previously. The response of PXN-treated hens to ACh was not significantly altered from that of vehicle-treated hens. The resistance generated in response to PE, an alpha 1-adrenergic agonist, in PSP-treated hens was greater than levels in vehicle-treated hens on d 1 and 3 and greater than the response seen in hens treated with PXN. Salbutamol, a beta 2-adrenergic agonist, at concentrations of 10(-7) to 10(-4) mol/kg caused an increase in resistance 1 and 3 d after PSP and a decrease on d 7. The responses to SAL were different in PXN-treated hens, as these hens demonstrated a lesser increase in resistance at concentrations of 10(-8) to 10(-7) mol/kg and a decrease in resistance at 10(-5) to 10(-4) mol/kg 1 d after administration of PXN. These observations indicate that response to vasoactive agents is altered in OP-treated hens and that responses differ between a compound capable of causing OPIDN (PSP) and a compound that only causes acute effects (PXN).

MeSH terms

  • Adrenergic Agents / pharmacology*
  • Animals
  • Brain / drug effects
  • Brain / enzymology
  • Carboxylic Ester Hydrolases / metabolism
  • Chickens
  • Cholinergic Agents / pharmacology*
  • Drug Interactions
  • Female
  • Hemodynamics / drug effects*
  • Insecticides / toxicity*
  • Motor Activity / drug effects
  • Organophosphorus Compounds / antagonists & inhibitors
  • Organophosphorus Compounds / toxicity*
  • Paraoxon / toxicity*
  • Random Allocation
  • Regional Blood Flow / drug effects
  • Verapamil / therapeutic use

Substances

  • Adrenergic Agents
  • Cholinergic Agents
  • Insecticides
  • Organophosphorus Compounds
  • phenylsaligenin cyclic phosphate
  • Verapamil
  • Carboxylic Ester Hydrolases
  • neurotoxic esterase
  • Paraoxon