The Effects of Paraoxon on Blood Pressure in the Anaesthetized and in the Conscious Rat

Abstract

1Intravenous administration of paraoxon tLg/kg) to anaesthetized rats induced longlasting, dose-dependent pressor effects. Only after injection of 825 jig/kg paraoxon was the pressor response followed by a depressor effect and a bradycardia that could be blocked by Nmethylatropine. Intracerebroventricular injection of paraoxon into anaesthetized rats also induced pressor effects. 2 In order to elucidate the mechanism of the pressor action rats were given dexetimide, Nmethylatropine, mecamylamine, phentolamine, prazosin, yohimbine, atenolol and metoprolol. If treatment with these drugs resulted in a low initial blood pressure, vasopressin was infused to elevate blood pressure to normal levels. The influence of adrenalectomy, pretreatment with reserpine and midcollicular transection was also examined. 3 The pressor effect of paraoxon was not influenced by N-methylatropine or mecamylamine. However, a combination of these drugs as well as dexetimide, phentolamine or prazosin combined with yohimbine, reduced or prevented the pressor effect. 4 In conscious rats the effects of paraoxon and the action of antimuscarinic drugs upon the pressor response were similar to those observed in anaesthetized animals. 5Acetylcholinesterase activities were measured in various brain regions and in whole blood. Paraoxon concentrations within the CNS were also measured. 6 It is concluded that the pressor effect of paraoxon in anaesthetized and conscious rats is mediated by a central mechanism, although a contribution of peripheral acetylcholinesterase inhibition in sympathetic ganglia to this pressor effect cannot be ruled out.

The Pressor Effects of Paraoxon in the Pithed Rat

“…We demonstrated that in intact animals the potency of various antagonists was dependent on the initial blood pressure (De Neef, Jordaan & Porsius, 1982). Phentolamine (30 mg/kg) reduced blood pressure but did not prevent the pressor effect by paraoxon in intact animals.…”

“…Hence in pithed rats the pressor response seems to be mediated by ganglionic muscarinic receptors. In contrast, the action of paraoxon in anaesthetized animals is mediated by ganglionic nicotinic receptors and is only mediated by ganglionic muscarinic receptors when nicotinic receptors are blocked (De Neef, Jordaan & Porsius, 1982).…”

“…This author could not prevent the pressor effect of physostigmine with phentolamine (up to 5 mg/kg). The paraoxoninduced tachycardia after treatment with aantagonists is probably due to blockade of presynaptic cardiac a-receptors and the inhibition of the reuptake of noradrenaline by these agents (Farnebo & Hamberger, 1971;Kirpekar & Puig, 1971;Cubeddu, Barnes, Langer & Weiner, 1974 & Porsius, 1982). In intact rats, however, the increase blood pressure was initiated by a stimulation of muscarinc receptors in the CNS, since Nmethylatropine was ineffective.…”

“…Paraoxon 275 lAg/kg induces a long-lasting pressor effect both in the intact anaesthetized and in the conscious rat (De Neef, Jordaan & Porsius, 1982).…”

“…sann (Dimhuber & Cullumbine, 1955) or physostigmine (Varagic, 1955;McEwen, 1968) also induce pressor responses, although higher doses are required. Recently we suggested that a peripheral component of the pressor effect induced by paraoxon in intact anaesthetized rats (De Neef, Jordaan & Porsius, 1982) may also exist. The present study was undertaken to investigate the mechanism of this peripherally mediated pressor effect.…”