The effect of eserine and neostigmine on the blood pressure of conscious rats

Small amounts of eserine salicylate (10 to 20 μg.) regularly caused a rise of blood pressure in non-anaesthetized rats. Neostigmine methylsulphate in doses from 1 to 10 μg./animal usually caused a fall of blood pressure, or no change was observed; only in a few experiments was a rise of blood pressure noted. The pressor effect of eserine was abolished by atropine and reduced or abolished by yohimbine and phentolamine. Adrenalectomy did not change the response to eserine. The present experiments do not contradict earlier statements that the pressor effect of eserine was due to the discharge of impulses from a centre or centres in the central nervous system

Factors influencing the hypertensive effect of eserine in the rat

Several factors influencing the hypertensive effect of eserine in the rat were investigated. Pretreatment with reserpine regularly depressed or abolished the hypertensive response to eserine. The slow intravenous infusion of either noradrenaline, dihydroxyphenylalanine or 5-hydroxytryptamine only occasionally restored the hypertensive effect of eserine in reserpine-treated rats. Bretylium and choline 2,6-xylyl ether bromide significantly depressed or even abolished the hypertensive effect of eserine. The effect of bretylium was stronger than that of choline 2,6-xylyl ether bromide. Cocaine was found to antagonize the action of bretylium on the response to eserine. In doses which significantly depressed the action of eserine bretylium did not inhibit the hypertension due to excitation of medullary centres induced by clamping the common carotid arteries. Lowering of body temperature abolished the hypertensive effect of eserine. Pretreatment with isopropylisoniazid did not antagonize the inhibitory action of reserpine on the hypertensive response to eserine. It is concluded that the present experiments indicate that the hypertensive effect of eserine in the rat is due to central activation of adrenergic nervous elements. Liberation of noradrenaline (and adrenaline) from the adrenals and from the blood vessels by eserine is an insignificant factor in producing the hypertensive response to eserine

The effect of enkephalins and of beta-endorphin on the hypertensive response to physostigmine in the rat.

1 Intracarotid injection of [Leu]enkephalin and [Met]enkephalin produced a dose-dependent biphasic change in blood pressure of the rat consisting of an initial shortlasting fall followed by a longlasting increase of blood pressure. Naloxone consistently depressed or abolished the effects of enkephalins on blood pressure. 2 Intracarotid injection of beta-endorphin only occasionally produced a hypotension, or did not produce any change in the blood pressure of the rat. 3 All three opioids ([Leu]enkephalin, [Met]enkephalin and beta-endorphin) significantly depressed or abolished the hypertensive response to intravenous injection of physostigmine. This depressive action of opioids was easily reversed by naloxone. 5 It is concluded that opioids depress the central cholinergic link implicated in the hypertensive response to physostigmine most probably by inhibiting acetylcholine and/or noradrenaline release in the structures relevant for the action of physostigmine on blood pressure of the rat. This interaction is realized through the activation of opioid receptor(s)

Effect of guanethidine, hemicholinium and mebutamate on the hypertensive response to eserine and catechol amines

Guanethidine, hemicholinium and mebutamate were used to study the site and mechanism of the hypertensive response to eserine in the rat. Guanethidine was found to block very effectively the hypertensive effect of eserine and to produce at the same time a very strong potentiation of the response to catechol amines. Hemicholinium, after a certain latent period, also blocked the effect of eserine, at the same time leaving the response to adrenaline and noradrenaline intact. Mebutamate was also found to block the effect of eserine. The results of the present experiments suggest that eserine produces a central adrenergic activation in the rat

The effect of substance p on the peristaltic reflex of the isolated guinea-pig ileum

The introduction of substance P into the lumen of the isolated guinea-pig ileum caused an increase in the number and amplitude of the peristaltic waves. In preparations in which the peristaltic reflex was abolished, by fatigue, by external or internal application of 5-hydroxytryptamine, or by lowering the temperature of the bath, the introduction of substance P into the lumen of the intestine restored peristalsis. This effect of substance P was absent in preparations in which the mucous membrane was removed. Hexamethonium abolished the effect of substance P on peristalsis. It is concluded that substance P acts on the afferent nervous elements of the peristaltic reflex arc, possibly on the sensory receptors