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  • Title: Relaxations of the isolated portal vein of the rabbit induced by nicotine and electrical stimulation.
    Author: Hughes J, Vane JR.
    Journal: Br J Pharmacol; 1970 Jul; 39(3):476-89. PubMed ID: 4394338.
    Abstract:
    1. A pharmacological analysis of the inhibitory innervation of the isolated portal vein of the rabbit has been made.2. In untreated preparations, transmural stimulation elicited a long-lasting relaxation at low frequencies (0.2-1 Hz); at higher frequencies a contraction followed by a prolonged after-relaxation occurred. Tetrodotoxin abolished the contractions but a higher dose was required to abolish the relaxations. Veratrine lowered the threshold of stimulation for producing relaxations in the untreated vein. The relaxations were unaffected by hyoscine or hexamethonium. They were reduced or altered by antagonists of alpha-adrenoceptors for catecholamines and by adrenergic neurone blockade. They were sometimes slightly reduced by antagonists of beta-adrenoceptors.3. In the presence of antagonists of alpha-adrenoceptors, electrical stimulation elicited relaxations which increased with frequency of stimulation and became maximal at 20-30 Hz. These relaxations were partially reduced by antagonists of beta-adrenoceptors, or by adrenergic neurone block; the antagonisms were more pronounced at the higher frequencies of stimulation. Noradrenaline also caused relaxations which were abolished by beta-adrenoceptor blocking drugs. Cocaine increased the sensitivity to noradrenaline by 7-8 fold after alpha-adrenoceptor blockade but had little or no effect on the relaxations induced by electrical stimulation at high frequencies.4. In the presence of antagonists of alpha- and beta-adrenoceptors, or adrenergic neurone blocking agents, or in veins taken from rabbits pretreated with reserpine, electrical stimulation elicited rapid relaxations which were greatest at 20-30 Hz. These relaxations were increased by veratrine and abolished by tetrodotoxin or by storing the vein for 9 days at 4 degrees C. They were unaffected by antagonists of acetylcholine, or by dipyridamole.5. Prostaglandins E(1), E(2) and F(2alpha) inhibited contractions elicited by electrical stimulation and noradrenaline, but in higher doses caused contractions themselves.6. Nicotine (10(-6)-10(-5) g/ml) relaxed the portal vein; higher concentrations elicited mixed inhibitory and excitatory effects. All these effects were abolished by tetrodotoxin, cocaine, hexamethonium or storage. The contractor effects were abolished by drugs or procedures that blocked adrenergic mechanisms.7. The relaxations produced by nicotine in untreated preparations and in veins from rabbits pretreated with reserpine were mediated mainly by a non-adrenergic non-cholinergic nervous mechanism. Relaxations induced by nicotine in the presence of antagonists of a-adrenoceptors were only partially antagonized by antagonists of f3-adrenoceptors.8. It was concluded that all the effects of nicotine and transmural stimulation were mediated by nerves. Part of the inhibitory effects was mediated by non-adrenergic, non-cholinergic nerves.
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