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In the isolated rat uterus, mescaline induces contractions that are notably antagonized by catecholamines, by beta-adrenergic stimulants and certain beta-adrenergic blocking agents as well as by chlorpromazine, amitriptyline and methysergide.
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Recently developed radioligand binding techniques permit direct investigation of the alpha- and beta-adrenergic receptors for catecholamines in a wide variety of tissues. These techniques allow the receptors to be quantitated, characterized, and studied under varying conditions of physiologic and pathophysiologic interest. They are providing fresh insights into the mechanisms by which endogenous catecholamines and other hormones regulate the properties of the adrenergic receptors and, in turn, control tissue sensitivity to catecholamine action.
Propranolol, alprenolol and sotalol given intraventricularly (ivc) to rats reduce depressing effects of isoprenaline (IPS) and antagonize stimulating effects of noradrenaline (NA). Phentolamine given by the same route of administration does not affect IPS action.
The effect of isoprenaline and three different beta-adrenergic blocking agents on blood eosinophilia was evaluated in the rat. Eosinopenic effect of isoprenaline was antagonized by intraperitoneal pretreatment with propranolol and by high but not low doses of practolol. Sotalol, a beta-blocker which in contrast to propranolol does not penetrate the blood-brain barrier, did not affect the eosinophil count when injected intraperitoneally, but produced a marked increase in number of circulating eosinophils following intracerebroventricular injection. Intraperitoneal administration of isoprenaline and propranolol as well as intracerebroventricular injection of sotalol did not affect eosinophil count in adrenalectomized or hypophysectomized rats. These results suggest that beta-adrenergic agents regulate the number of circulating eosinophils through a central mechanism and that presence of both hypophysis and adrenal glands is required for this action.
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The soleus muscle of a guinea-pig was dissected out under pentobarbitone anaesthesia and mounted on a holder in an organ bath containing Krebs solution. The tendon was attached to a force transducer and subtetanic contractions were evoked by electrical field stimulation (0.5 ms pulses at 10-12 Hz for 1.5 or 3 s every 22 s). The experiments were performed at 37 degrees. Terbutaline, a selective agonist at beta2-adrenoceptors, reduced the force of subtetanic contractions in a dose-dependent manner, the EC50 being 0.2 muM. The reduction was due to a lessened degree of fusion. The results conform to previous in vivo studies.
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Secondary and tertiary amino homologs of the title compounds have been prepared, bearing an N-isopropyl group. In peripheral evaluation, certain members of the series exhibited beta-adrenergic agonist effects of lower activity than isoproterenol. N-Methyl-N-isopropyl-5,6-dihydroxytetralin exhibited marked properties consistent with its being an alpha agonist, and it is concluded that introduction of considerable bulk about the nitrogen of a catecholamine does not a priori destroy alpha-agonist effects. The compounds qualitatively paralleled the effects of dopamine in assays based upon direct intrastriatal administration in rats, although they were less potent than dopamine.
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The beneficial effect of stimulators of beta-adrenergic structures (Myophedrin on the haemodynamics and the inotropic function of the myocardium was demonstrated experimentally (in 12 rabbits) and clinically (in 53 patients with ischaemic heart disease). A positive effect of the treatment was noted in 45.5% of those patients in whom ischaemic heart disease manifested itself in angina decubitus and angina of effort.
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In the author's experience, the longterm treatment of chronic obstructive lung disease should be supplemented by continuous selective stimulation of the adrenergic beta-receptors in the smooth bronchial muscles. The following procedure is recommended: inhalation of 15 min 3 times daily using an adequate aerosol with a powered nebulizer (Pari-Privat), with 2-3 ml Tyloxapol carrier solution or saline with 5 drops salbutamol.
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Frequency of exercise-induced asthma has been studied in 75 unselected asthmatic patients (adults and children) by measuring the forced expiratory volume at one second (FEV1) and the vital capacity (VC) before and after a treadmill exercise, continued until heart rate was at least equal to 80 p.cent-85 p.cent of maximum heart rate. In 19 subjects (25 p.cent), a more than 20 p.cent decrease from control value of FEV1 was recorded ten minutes after exercise ended. Exercise-induced bronchial obstruction was relieved by a beta adrenergic bronchodilator aerosol inhalation. In the group of 19 subjects having exercise-induced asthma, a significant positive correlation was found between pre-exercise FEV1 values and post-exercise FEV1 decreases. In the whole group of 75 subjects exercise-induced asthma was related to the severity of asthma and not to other clinical or physical characteristics of the subjects. From the data of other authors it appears that frequency of exercise-induced asthma is variable. The reasons of those differences are discussed.
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