Possible Role of Vasopressin in the Thermoregulatory Response to Chlorpyrifos in the Rat

Abstract

Arginine vasopressin is a naturally occurring antipyretic which is released into the CNS to prevent excessive elevations in body temperature during fever. Circulating levels of arginine vasopressin may also have a role in the tonic control of body temperature. We have found that the organophosphate insecticide chlorpyrifos will raise blood pressure and lower body temperature in the rat. Because arginine vasopressin is a potent hypertensive agent and is capable of lowering core temperature, we suspected that arginine vasopressin may be involved in the thermoregulatory response to chlorpyrifos. To this end, core temperature and motor activity of male and female Sprague-Dawely rats were monitored before and after treatment with the corn oil vehicle or chlorpyrifos (15 mg/kg in females; 30 mg/kg in males; oral) concomitant with injection of a saline vehicle or a type 1 arginine vasopressin antagonist (20 mg/kg in females; 30 mg/kg in males; intraperitoneally). Rats dosed with chlorpyrifos and saline underwent a 2-3 ae reduction in core temperature Ͼ50% decrease in motor activity. The V1 antagonist attenuated the hypothermic effect of chlorpyrifos in both sexes. Chlorpyrifos-induced inhibition in motor activity was unaffected by the V1 antagonist. In another experiment, the V1 antagonist (30 mg/kg) was co-administered with saline or 0.2 mg/kg oxotremorine, a muscarinic agonist that stimulates a heat loss response and partially mimics the effects of chlorpyrifos. The V1 antagonist attenuated the hypothermic effect of oxotremorine in both sexes. Plasma arginine vasopressin levels were determined in male rats 3 hr after corn oil or 30 mg/kg chlorpyrifos. There was no significant effect of chlorpyrifos on plasma levels of arginine vasopressin. That the V1 antagonist blocked the hypothermic effect of chlorpyrifos suggests that the thermoregulatory response to chlorpyrifos is mediated by central and/or systemic vasopressin release. The lack of a significant increase in plasma vasopressin after chlorpyrifos suggests that localized release of vasopressin may be involved in the thermoregulatory response to chlorpyrifos.

Simultaneous telemetric monitoring of the circadian changes in core and BAT temperature in rats: Endogenous vasopressin may contribute to reduced BAT themogenesis and body temperature in the light phase of the circadian cycle

“…Few studies have also assessed the mechanism by which AVP evokes the drop in normal body temperature (Shido et al, 1984;Paro et al, 2003). We have found that chlorpyrifos-induced hypothermia was blocked by administration of V 1 receptors antagonist, suggesting that the thermoregulatory response to chlorpyrifos is mediated by central and/or systemic AVP release (Yang and Gordon, 2002).…”

Physostigmine-induced hypothermic response in rats and its relationship with endogenous arginine vasopressin

“…The data of this study suggest that endogenous AVP could be involved in PHYinduced hypothermic processes, because PHY can increase plasma AVP and AVP V1 receptor antagonist attenuated the hypothermia effect of PHY in the rat. This may be a novel mechanism of action for anti-ChE drugs such as PHY and related agents including organophosphates (Yang and Gordon 2002).…”

“…Furthermore, cholinergic stimulation of the hypothalamic area has been shown to elicit the release of arginine vasopressin (Michels et al 1991;Raber and Bloom 1996). Yang and Gordon (2002) found that chlorpyrifos-induced hypothermia was blocked by administration of an AVP V 1 receptor antagonist, suggesting that the thermoregulatory response to chlorpyrifos is mediated by central and/or systemic AVP release (Yang and Gordon 2002). …”

“…We have found that AVP is involved in mediating the hypothermic effects of chlorpyrifos (an organophosphate insecticide) in male and female rats (Yang and Gordon 2002). Chlorpyrifos is an anticholinesterase (anti-ChE) that irreversibly inhibits acetylcholinesterase activity leading to central and peripheral cholinergic stimulation.…”

ADHD-like behaviour in the offspring of female rats exposed to low chlorpyrifos doses before pregnancy / Ponašanje nalik ADHD-u u potomaka ženki štakora izloženih niskim dozama klorpirifosa prije trudnoće

“…Group 4 (three animals of the same age and weight) received a single dose of 30 mg kg -1 CPF on gestational day 6. This dose has been used in a number of studies as a sub-toxic acute dose that does not cause immediate symptoms of poisoning but can lead to some adverse effects (14,15). Control females (group 5) received pure oil.…”