Summary1. In anaesthetized rats, intravenous administration of cannabis extract (10 mg/kg), Al-tetrahydrocannabinol (THC) (05 mg/kg) and A6-THC (0-5 mg/kg) caused a reduction in systemic blood pressure, pulse rate and respiratory rate. 5. Both cannabis extract and A'-THC potentiated reflex vasodilatation and direct vasoconstriction in the hindlimb induced by intravenous noradrenaline in the cat; they reduced reflex hindlimb vasoconstriction elicited by histamine, acetylcholine or bilateral carotid occlusion. 6. Tolerance to these cardiovascular and respiratory effects of cannabis extract developed in rats which had been treated i.p. with the extract at (50 mg/kg) per day for 14 days.
. (1976). Thorax, 31,[720][721][722][723]. Bronchodiator effect of Al-tetrahydrocannabinol administered by aerosol to asthmatic patien. Ten volunteer inpatient asthmatics in a steady state were given a single inhalation of an aerosol (63 ,ul) delivered in random order, on each of three consecutive days, in the laboratory of a respiratory unit. Before, and for one hour after treatment the pulse, blood pressure (lying and standing), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak flow rate (PFR), and self-rating mood scales (SRMS) were recorded. Treatments were placebo-ethanol only; Al-tetrahydrocannabinol (THC) 200 ,Mg in ethanol; or salbutamol 100 Mug (Ventolin inhaler), administered double blind. Salbutamol and THC significantly improved ventilatory function. Maximal bronchodilatation was achieved more rapidly with salbutamol, but at 1 hour both drugs were equally effective. No cardiovascular or mood disturbance was detected, and plasma total cannabinoids at 15 minutes were undetectable by radioimmunoassay. The mode of action of THC differs from that of sympathomimetic drugs, and it or a derivative may make a suitable adjuvant in the treatment of selected asthmatics.
Langley (1900) originally suggested that the postganglionic sympathetic nerves which innervate the cat nictitating membrane are derived from cell bodies in the superior cervical ganglion. This contention was supported by Thompson (1961) Rand (1959) that adrenergic nerves contain a cholinergic mechanism which is functionally related to the release of noradrenaline.
METHODSA total of nine young adult cats of either sex was used in this study. In two cats right superior cervical ganglionectomy was performed under ether anaesthesia with recovery ; the animals were killed respectively 2 days and 28 days after sympathectomy.The nictitating membrane of the cat is retracted by two smooth muscle sheets-the inferior and the medial muscles-both arising from the peribulbar fascia (Acheson, 1938). Samples of smooth muscle can be readily obtained via an incision through the orbital fascia after fully exhibiting the nictitating membrane by drawing it laterally across the eye. Specimens from intact and sympathectomized animals were processed as follows.
Hukovic (1961) described the isolated hypogastric nerve-vas deferens preparation from the guinea-pig and its response to nerve stimulation and to drugs. This preparation has often been used for physiological and pharmacological research, but little has been reported about the vas deferens of the rat. It was thought desirable, therefore, to compare the vas of this species with that of the guinea-pig in some detail in order to reveal any important differences in their respective morphology and responses to drugs. Particular attention was directed towards the ability of certain 2-halogenoalkylamine compounds to affect the responses of the vas deferens to added neuro-transmitters and to stimulation of the hypogastric nerve.
METHODS
Isolated preparationWistar rats weighing 300 g and guinea-pigs weighing 250-350 g were used. The nerve and muscle were prepared as described by Graham & Katib (1967) and mounted in a solution of the following composition: NaCl 7.6 g, KCl 0.42 g, CaC12 0.24 g, MgSO47 H20 0.12 g, NaHCO3 1 g, glucose 1 g in 1 1. The nerve was stimulated from a SD-5 Grass apparatus with square wave pulses of 0.5 msec duration, frequency range 5-100 shocks/sec every 2 min at a supramaximal voltage in the range 3-5 V. When determining the effect of variation of frequency on any one tissue a constant number of shocks (200) was delivered every 2 min. The two frequencies of 10/sec and 80/sec were used routinely for " slow " and " fast" stimulation respectively. Transmural stimulation was delivered by means of the electrode described by Birmingham & Wilson (1963) with square pulses of 0.1 msec, frequency 25/sec, 80 V for rats, 100 V for guinea-pigs; 250 shocks every 4 min or as needed. Drugs were added to the bath in some experiments. Some animals were injected intraperitoneally with reserpine 5 mg/kg 48 hr and again 24 hr before removal of the vas deferens. The drugs used were:Group 1: noradrenaline bitartrate (NA); isoprenaline sulphate; dibenamine; N-ethyl-N-1-naphthylmethyl bromoethylamine hydrobromide (SY28); N-dimethyl-phenylethylamine hydrobromide (L2, Graham & James, 1961) and their ethanolamines; pheniprazine hydrochloride; pronethalol.Group 2: acetylcholine chloride (ACh), physostigmine salicylate; 1-hyoscine hydrobromide; atropine sulphate; hemicholinium (HC3); mecamylamine hydrochloride; pempidine tartrate; hexamethonium chloride (C6); procaine hydrochloride.
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