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
Wc. Mccain et al., 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, Journal of toxicology and environmental health, 48(4), 1996, pp. 397-411
Blood samples and vascular segments from the ischiadic artery of hens
treated with either cyclic phenyl saligenin phosphate (PSP; 2.5 mg/kg,
im) or paraoxon (PXN; 0.1 mg/kg, im) in the presence or absence of ve
rapamil, a calcium channel antagonist (7 mg/kg, im, given 4 consecutiv
e days beginning the day before PSP or PXN administration), were exami
ned 1, 3, 7, and 21 d after PSP or PXN administration in order to dete
rmine the contribution of catecholamines and peripheral blood vessel p
hysiology and morphology to organophosphorus-induced delayed neuropath
y (OPIDN). The levels of plasma catecholamines were measured by high-p
erformance liquid chromatography (HPLC) and indicated a different effe
ct with PSP, which causes OPIDN, and PXN, which does not. PSP treatmen
t elevated the levels of norepinephrine and epinephrine throughout the
study, while PXN treatment depressed the levels of these catecholamin
es. Verpamil treatment attenuated the OP response by approximately 50%
for both compounds. Ischiadic vessel segments were isolated from OP-t
reated hens and perfused at a constant flow rate of 12 ml/min, then ex
amined for their response to potassium chloride (KCl, 3 x 10(-3) M), a
cetylcholine (ACh), phenylephrine (PE), an alpha(1) adrenergic agonist
, and salbutamol (SAL), a beta(2) adrenergic agonist. Agents were deli
vered in concentrations of 10(-8) to 10(-3) M. Vascular segments did n
ot 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 P
SP or PXN. This reduced response was not altered by the presence of ve
rapamil. innervation of the peripheral vasculature was unchanged after
OP treatment. This study indicates that plasma catecholamine levels c
ould be differentially altered by treatment with OPs that do and do no
t cause OPIDN and suggests that the alterations involve intracellular
calcium. In contrast, vascular response of the ischiadic artery was al
tered following OP treatment, but the effect was not specific for the
neuropathy-inducing OP, PSP, and response was not mediated by Ca2+, no
r was it the result of autonomic nerve deterioration.