The effects of paraoxon on blood pressure in the anaesthetized and in the conscious rat.

1 Intravenous administration of paraoxon (150-825 mug/kg) to anaesthetized rats induced long-lasting, dose-dependent pressor effects. Only after injection of 825 mug/kg paraoxon was the pressor response followed by a depressor effect and a bradycardia that could be blocked by N-methylatropine. 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, N-methylatropine, 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.5 Acetylcholinesterase 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.