Catecholamine concentrations and contractile responses of isolated vessels from hens treated with cyclic phenyl saligenin phosphate or paraoxon in the presence or absence of verapamil.
Blood samples and vascular segments from the ischiadic artery of hens treated with either cyclic phenyl saligenin phosphate (PSP; 2.5 micrograms/kg, im) or paraoxon (PXN; 0.1 micrograms/kg, im) in the presence or absence of verapamil, a calcium channel antagonist (7 micrograms/kg, im, given 4 consecutive days beginning the day before PSP or PXN administration), were examined 1, 3, 7, and 21 d after PSP or PXN administration in order to determine the contribution of catecholamines and peripheral blood vessel physiology and morphology to organophosphorus-induced delayed neuropathy (OPIDN). The levels of plasma catecholamines were measured by high-performance liquid chromatograpy (HPLC) and indicated a different effect with PSP, which causes OPIDN, and PXN, which does not. PSP treatment elevated the levels of norepinephrine and epinephrine throughout the study, while PXN treatment depressed the levels of these catecholamines. Verapamil treatment attenuated the OP response by approximately 50% for both compounds. Ischiadic vessel segments were isolated from OP-treated hens and perfused at a constant flow rate of 12 ml/min, then examined for their response to potassium chloride (KCl, 3 x 10(-3) M), acetylcholine (ACh), phenylephrine (PE), an alpha 1 adrenergic agonist, and salbutamol (SAL), a beta 2 adrenergic agonist. Agents were delivered in concentrations of 10(-8) to 10(-3) M. Vascular segments did not respond to ACh or SAL at any concentration used. Vessels displayed a significant reduction in contractile response to both KCl (3 x 10(-3) M) and PE (10(-8) to 10(-3) M) 3 and 21 d after exposure to either PSP or PXN. This reduced response was not altered by the presence of verapamil. Innervation of the peripheral vasculature was unchanged after OP treatment. This study indicates that plasma catecholamine levels could be differentially altered by treatment with OPs that do and do not cause OPIDN and suggests that the alterations involve intracellular calcium. In contrast, vascular response of the ischiadic artery was altered following OP treatment, but the effect was not specific for the neuropathy-inducing OP, PSP, and response was not mediated by Ca 2+, nor was it the result of autonomic nerve deterioration.
McCain
W C
WC
Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061-0442, USA.
Flaherty
D M
DM
Correll
L
L
Jortner
B
B
Ehrich
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000097:blood; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000633:toxicity; D015415:Biomarkers / Q000097:blood; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002265:Carboxylic Ester Hydrolases / Q000097:blood; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood*; D005260:Female; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood*; D010261:Paraoxon / Q000008:administration & dosage / Q000633:toxicity; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011897:Random Allocation; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D001592:Benzyl Alcohols; D015415:Biomarkers; D002121:Calcium Channel Blockers; D007306:Insecticides; D010656:Phenylephrine; D011189:Potassium Chloride; D014700:Verapamil; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D000110:Acetylcholinesterase; C010631:salicyl alcohol; D000109:Acetylcholine; D010261:Paraoxon; D000420:Albuterol; D009638:Norepinephrine; D004837:Epinephrine