After the transmembrane potential and spontaneous contraction of the isolated atrium of rabbit had been abolished by the addition of 10-5 g/ml of reserpine, the addition of adrenaline or noradrenaline restarted the contraction but only washing of the preparation did not so (1, 2). In contrast to the depletion over ninety per cent of the extractable noradrenaline in the atrium from rabbit which had received 1.0 to 5.0 mg/kg of
In the foregoing report Matsuo and Tachi (1) showed that though the isolated atrium of rabbit which was beating in vitro took up considerable amounts of noradrenaline added to the bath fluid, the content of noradrenaline of the restarted atrium by addition of nor adrenaline did not significantly differ from the reduced content of noradrenaline of the atrium which was ceased to beat by addition of 10 of reserpine.From the results the authors suggested that the restarting effect derived from the pharmacological action of the catecholamine and not from the biochemical binding of catecholamine to the storage site. The role of the dopa-decarboxylase in noradrenaline synthesis was substantiated with the demonstration of the conversion of dopa and of dopamine to n9radrenaline (2-3). In this report the effects of dopa and dopamine were studied on the spontaneous contraction, transme_mbrane potentials and content of noradrenaline in the isolated rabbit's atrium which had been depressed or abolished the spontaneous activity and depleted the content of noradrenaline by reserpine.
The depressant effect of reserpine on the spontaneous contraction and transmem brane potentials of the isolated atrial preparation of rabbit has been described in detail in the previous reports (1-4). A rise instead of fall in the blood pressure due to reserpine, the reserpine reversal, was demonstrated in the dog and cat pretreated with monoamine oxidase inhibitors (5, 6). Shore and Brodie (7) found that administration of reserpine to rabbits pretreated with iproniazid resulted in the sympathetic excite ment. However, Eltherington and Horita (6) observed no sign of the reserpine reversal after amphetamine in mice. Shimamoto and Torii (8) observed that pretreatment of rabbits with iproniazid reversed the response of the blood pressure and the behavior to the intravenous injection of reserpine.Toda (9) of this laboratory observed that the application of monoamine oxidase inhibitors to the isolated rabbit atrium did not reverse, but delayed onset of the effect of reserpine on the atrial transmembrane potential.Recently, Goldberg and Shideman (10) have shown that the intraperitoneal injection of a monoamine oxidase inhibitor, SKF-385, depletes the myocardial noradrenaline in cats, and conversely, accumulates it in rats. Matsuo (11) . of this laboratory has shown that the application of SKF-385 to the isolated atrium of rabbit does not produce sig nificant changes in the noradrenaline content of the atria. Pepeu et al. (12) demonstrated that the pretreatment of the guinea-pig atrium with iproniazid prevented the spon taneous depletion of noradrenaline from this tissue, but that with PIH did not so.To elucidate the mechanism of the reserpine reversal on the spontaneous contraction of the isolated atrial preparation of rabbits, the effects of the monoamine oxidase inhibitors on the depressant action of reserpine were studied. METHODSAlbino rabbits, 2.0 to 2.5 kg of body weight, were used. Animals were killed by cutting both common carotid arteries. Immediately thereafter the heart was extirpated, and the atrium was separated from the ventricle.The atrial preparation was
We have already reported on the action of drugs such as acetylcholine, epinephrine, reserpine, cardiac glycosides, antiarrhythmic agents, veratrine and chelating agents on the intracellular action potentials recorded from the ventricular muscle, sinoatrial node and the non-pacemaker atrial fibers of the isolated rabbit heart using the ultramicro electrode method (1-3).The present experiments were undertaken to determine the influences of anticholin esterases on the membrane potentials of the isolated rabbit atrial muscle exhibiting spon taneous beating. Observations on the antagonisms between the action of anticholinesterases and of cholinesterase reactivators on the membrane potentials were also designed . METHODSAs described previously (1-3), the experiments were carried out on the right incised atrium of rabbits. The endocardial surface of the dissected right incised atrium was pinned on a cork block mounted in a lucite chamber containing about 10 ml of oxygen saturated Tyrode solution at approximately 30°C. The drugs were added directly to Tyrode solution in the chamber and their concentrations were expressed in terms of w/v (g/ml). Recordings of the transmembrane potentials from non-pacemaker and pacemaker areas were taken by the intracellular microelectrode. The recording electrode , less than 1 µ in diameter, drawn from special glass capillary tubing and filled with 3 M-KCI , having low resistance (8-20 MQ), was selected and fixed on the arm of a micromanipulator . A chloride silver wire was pushed into the shaft of the electrode and was soldered onto flexible strand thereby connected to a d.c. amplifier with an input cathode follower of low grid current and reduced grid-earth capacity. The output of the amplifier was led to a cathode-ray oscilloscope and ink-writing recorder (Sanei's Type MPA-204) .
Whenever any central effects of catecholamine are studied, the possibility that the amines act indirectly by virtue of their effects upon cerebral blood vessels and flow merits some consideration. The effects of the amines upon these structures were the subjects of a number of research work since 1900's. As might be anticipated, there are many contradictory results in which adrenaline delates the cerebral vessels, constricts them, does both or does neither. Recently, Ingvar and Soderberg (1) have studied the effects of adrenaline and noradrenaline on cerebral flow in cat by measuring the rate of venous outflow of the cannulated superior sagittal sinus. They found that the intra venous adrenaline or noradrenaline produced an increase of the cerebral blood flow, ap parently secondary to the pressor response, and that noradrenaline produced less increase of the flow than adrenaline, and also that the intracarotid injection of noradrenaline caused a brief cerebral vasoconstriction before the pressor effect by the amine manifested, whereas the same procedure of adrenaline caused no initial constriction.Though there is no reason to assume that catecholamines act directly or indirectly on the specific mechanism in the brain, the present experiment was designed to elucidate the correlation between the mode of the cerebral vessels an.d the central sympathetic activity in response to the intravenously administered adrenaline or noradrenaline in the anesthetized dog following the technique of the cross circulation of their head (2). Recently, Polet and De Schaepdryver (3) have devised a modified method of the isolation of head circulation, in which the head circulation of the recipient is completely separated from that of the body with a maintenance of a normally functioning spinal cord. METHODS Dog, weighing 5 to 15 kg of body weight, was anesthetized with the intraperitoneal injection of 50 to 70 mg/kg of amytal sodium. Two dogs were prepared for one experi ment, one dog being donor and the other being recipient. By the longitudinal medico anterior incision of the skin in the neck the anterior neck muscles, trachea and eso phagus were divided with cautery ; the common carotid arteries and the vagus nerves were preserved intact. The trachea was incised in both dogs and was cannulated. The anterior surface of the seventh cervical vertebra was exposed. The soft tissues overly ing the surface of the vertebra were divided. The vertebral arteries and veins of the recipient, so far exposed, were ligated. The ascending cervical artery and vein were
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