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Volume 15 (1965)
- Issue 4 Pages 327-
- Issue 3 Pages 201-
- Issue 2 Pages 91-
- Issue 1 Pages 1-
Volume 15, Issue 1
Displaying 1-11 of 11 articles from this issue
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AKIRA UENO, MASAMICHI MATANO, YOSHIRO NAKAZAWA1965 Volume 15 Issue 1 Pages 1-9
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSThe anaphylactic manifestation in the atrium isolated from a sensitized guinea pig is an increase in the contractile tension and in the beat rate (1, 2). Although the reaction is similar to the response of histamine, serotonin and adrenaline, it has not been blocked by antihistaminics (3) or DCI (4). So it is probable that the reaction occurs as a primary effect of anaphylactic manifestation taking place in cardiac muscle fibers (1).. It was also found in our laboratory that the time course of repolarization of the transmembrane action potential of proper atrial fiber of guinea pig is prolonged during anaphylaxis (5, 6). Furthermore, records of action potential of specialized fibers in the sinoatrial node during anaphylaxis showed the increased slope of the prepotential without any changes in its height (4). Similar observation of action potential change in intestinal segment during anaphylaxis has also been reported by Katsh and Marshall (7). So the prolongation of action potential duration in muscle fiber seems to be a ubiquitous change occurring in the anaphylactic manifestation.
On the other hand, some results have been presented indicating that the duration of the action potential is one factor determining the contractility: changes in temperature alter both electrical and mechanical activity (8, 9), and tension and action potential duration decrease progressively as frequency increased in the rat atrium (9) and the guinea pig atrium (6), and several studies reported a change of comparable magnitude in action potential duration and contractility (10-13). These observations, however, do not imply that change in contractility must be associated with changes in action potential duration: that has also been confirmed in a number of studies (14-16). Therefore, the use of intracellular microelectrode technique to study electrical activity of cardiac muscle fibers has not provided much new information on the relationship between electrical and mechanical responses, and further investigation with different approaches is needed to discuss mechanism of the inotropic effect.
In order to obtain further informations on the mechanism of anaphylactically induced inotropic action it seemed of interest to study the effect on contraction when muscle membrane is depolarized in the definite level. This can be done by studying the participation of anaphylactic manifestation on contractures of auricle preparation induced by application of depolarizing potassium chloride solution. However, attitudes of most drugs on the potassium contracture have not been reported with a few exception (17-19). The authors have also studied the effects of various agents having an inotropic action in guinea pig atria on the potassium contracture.View full abstractDownload PDF (387K) -
YOSHIRO NAKAZAWA, AKIRA UENO1965 Volume 15 Issue 1 Pages 10-18
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSDuring the investigation of atrial anaphylaxis, positive inotropic effects of various drugs have been compared with that of the anaphylactic manifestation in the isolated guinea pig atria, it was observed that thiamine derivatives increased the contractile force of the atrium. Thiamine propyl disulfide (TPD) and thiamine tetrahydrofurfuryl disulfide (TTFD) are allithiamine derivatives discovered by Fujiwara (1), having a marked vitamin B1 action on the process of glucose and lipid metabolism in the body because these compounds readily penetrate the living tissue. Clinically these drugs are used for the treatment, not only of vitamin B, deficiency but also, of various heart diseases, postoperative intestinal paralysis etc, and their effects have been reported (2-4). However, nothing more than effect of these drugs on energy metabolism of the cardiac muscles has been known. Very few investigation has been attempted to elucidate the nature of their clinical effectiveness. Katsura (5) has reported the increased amplitude of the isotonic contraction and prolongation of the repolarization phase of the action potential of cardiac muscle fibers in the isolated toad heart by TPD. H. Simonnet et al. (6) have made a comparative study of pharmaco-dynamic action of thiamine and TPD but they could not obtain any findings to explain the effect of TPD.
In the present study, attempts were made to describe a positive inotropic action of the thiamine derivatives and to compare their influences on transmembrane action potential pattern, potassium contracture and Ca uptake with those of other drugs that act inotropically in guinea pig atria in vitro.View full abstractDownload PDF (418K) -
HIROSHI TAKAGI, RYUICHI ISHIDA1965 Volume 15 Issue 1 Pages 19-29
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSThe authors have reported in the previous papers that tetrabenazine antagonizes morphine analgesia in mice (1) and that it has depressive effects on some afferent pathways in the central nervous system in rabbits and cats, like those of morphine (2).
The questions arise whether the antagonistic effect by tetrabenazine of the central effects of morphine can be recognized in other species besides mice, whether all of the depressive actions of morphine on the afferent pathways of the central nervous system are suppressed by the tetrabenazine pretreatment, and whether tetrabenazine may owe its antagonistic action against morphine to its ability to deplete the catecholamines and serotonin levels in the brain.
The purpose of this study was to investigate these questions using the electrophysiological techniques.View full abstractDownload PDF (443K) -
HIROSHI HIKOSAKA, MOTOHATSU FUJIWARA, NOBORU TODA1965 Volume 15 Issue 1 Pages 30-40
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSSince the report of hypotensive effect without central depression of 10-methoxydeserpidine (1), several investigators have studied the mode of its action. Mir and Lewis (2) have demonstrated the gradually developing fall of blood pressure following 10-methoxydeserpidine in cats, rabbits and rats. However, unlike reserpine, 10-methoxydeserpidine does not produce significant depletion of brain and heart noradrenaline in mice (3). Recently, Higuchi et al. (4) and Toda et al. (5) in this laboratory have reported that the intravenous or intracarotid injection of 5 to 10 mg/kg of 10-methoxydeserpidine in rabbits produces considerable depletion of catecholamines in the brain, heart and adrenal glands. The latter authors (5) have further shown that the intravenous injection of 10 mg/kg of 10-methoxydeserpidine to rabbits results in a sustained rise of the skin temperature of the ear without modifying the rectal temperature, and that 1 mg/kg of reserpine produces a similar but longer-lasting rise of the ear skin temperature with a significant fall of the rectal one. They suggested that the skin temperature rise might be due to an increased blood flow in the ear. The earlier observation by Guthrie (6) that the inhalation of amyl nitrite, a potent coronary vasodilator, in man produced a flushing of the skin with a temperature rise and a blood flow increase in the neck and face indicates a resemblance of the effects of amyl nitrite to those of 10-methoxydeserpidine and reserpine.
The ECG changes in rabbits and dogs following the posterior pituitary extract were described by Melville (7), Hecht and Nadel (8), and Gruber and Kountz (9). They observed an elevation of ST level, and increase in height of T wave and the ventricular extrasystole with a concomitant blood pressure rise, and ascribed these ECG changes to the anoxia of the heart secondary to the coronary vasoconstriction.
The present report describes the effect of 10-methoxydeserpidine on ECG changes in rabbits following the intravenous administration of vasopressin in an attempt to confirm the coronary vasodilating action of 10-methoxydeserpidine.View full abstractDownload PDF (483K) -
GEORGE NAKATANI1965 Volume 15 Issue 1 Pages 41-47
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSIt was reported previously (1) that an increase in heart phosphorylase a following the intravenous administration of adrenaline in a dose of 10.0 μg/kg was less than that following 1.0 μg/kg, and that atropinization or vagotomy potentiated the phosphorylaseactivating action of adrenaline. In addition, a significant elevation of heart phosphorylase a was maintained for 2 hours after the injection of 1.0 μg/kg of adrenaline. From the results, it was suggested that the reflectively released endogenous acetylcholine inhibited the phosphorylase-activating action of adrenaline, and that the long-lasting elevation of heart phosphorylase a even after disappearance of the positive inotropic action of adrenaline was related to the uptake or storage mechanism of adrenaline in the heart tissue.
Many investigators (2-6) demonstrated that the positive ino- and chrono-tropic responses to exogenous adrenaline of the heart were closely related to the activation of formation of cyclic 3', 5'-AMP with subsequent conversion of phosphorylase b to a. The finding (7) that injection of ganglionic stimulating agents such as DMPP and McNeil-A-343 produced an increase in heart phosphorylase a with concomitant hypertension and increase in cardiac contractile force may suggest a relationship between the level of circulating catecholamine endogenously liberated and the activity of phosphorylase in the heart. However, there are controversial reports regarding the effect of reserpine on heart phosphorylase activity: no significant change (4, 8), increase (6), and decrease (9). This is incompatible with the concept that there is a positive correlation between the amount of endogenous catecholamine and cardiac phosphorylase a activity.
The inhibitory effects of injected acetylcholine and vagal stimulation on the activity of heart phosphorylase a in open-chest rats have been demonstrated by Hess et al. (7). In an attempt to study the effect of endogenous acetylcholine on heart phosphorylase a, anticholinesterase agents were injected to spinal rats. Unexpectedly, physostigmine increased the activity of the heart enzyme. Further, combined administration of adrenaline and physostigmine, both of which otherwise activated the heart enzyme, resulted in an inhibition of the enzyme activity.View full abstractDownload PDF (317K) -
HIDEMASA YAMASAKI, KOITI ENDO1965 Volume 15 Issue 1 Pages 48-56
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSThe release of histamine in anaphylaxis has been shown to be blocked by anoxia and various enzyme inhibitors considered to interfere with metabolic energy-yielding processes (1-5). Several recent works (5-8) have indicated that glycolysis constitutes one of the sources of energy, at least under anoxic conditions, from the fact that presence of glucose prevents blocking actions both of anoxia and of inhibitors which interfere the oxidative metabolim. In our previous paper (3) reporting the enhancing effect of succinate on aerobic histamine release by antigen from sensitized guinea-pig lung tissue, a slight but similar effect of glucose was noted. This glucose effect was confirmed by Diamant (9, 10) not only in guinea-pig but in rat lung, while in the latter species succinate had no effect. Despite these discrepancies, some of energy required for the processes seems, even under aerobic conditions, to be delivered via glycolysis in both species. Therefore, it is interesting to investigate the influences on the glucose effect of substances which may interfere the metabolism of glucose or its transport across the cell membrane, under aerobic and anaerobic conditions. 2-Deoxyglucose, phlorizin, insulin and ouabain were chosen for the present study as such substances. This paper also present observations on the comparative effects of succinate and glucose on the anaphylactic release of histamine, along with the oxygen uptake, from the minced lung tissues of guinea pig and rat.View full abstractDownload PDF (419K) -
KOTOBUKI HANO, HEITAROH IWATA, NOBUYOSHI IWATA, HIROSHIGE HONMA1965 Volume 15 Issue 1 Pages 57-61
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSA difference has been demonstrated between the total catecholamine contents of the atrium and the ventricle in the dog heart (1) and in the rabbit heart (2): the level being higher in the atrium than in the ventricle.
Moreover, a depletion of catecholamine in various tissues after reserpine injection was reported by many workers (3-6) and several studies (7, 8) have indicated that the heart is capable of taking up noradrenaline from the circulating blood.
Recently, Sakaguchi et al. (9) assayed the adrenaline and noradrenaline content of the rat heart at various times after reserpine administration and observed that the noradrenaline content of the rat heart was usually reduced by 6 hours ter reserpine administration, but began to increase 24 hours after the reserpine treatment, and had returned to normal within a month. Other workers (10) showed that maximal depletion of cardiac catecholamine occurred 4 hours after a single dose of reserpine to the rat, and the normal level was not regained until about 10 days after the dose.
However, no experiments were made on the difference between the recovery of the catecholamine contents of the atrium and the ventricle after reserpine administration.
The purpose of the present studies was to obtain information on this point.View full abstractDownload PDF (188K) -
SHOICHI IMAI, HIROSHI MURASE, MAKOTO KATORI, MASAHIRO OKADA, TATSURO S ...1965 Volume 15 Issue 1 Pages 62-71
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSAccording to the prevailing opinion of today about the structure-activity relationship of cardenolides and bufadienolides, the structural requirements for the characteristic cardiotonic action of these compounds can be summarized as follows: cis-fusion of the C and D rings, hydroxyl groups in positions 3β and 14β, and a five- or six-membered unsaturated lactone ring having β-configuration at C14 (1). Most of the experimental data referred to as evidences supporting this opinion have come, however, from the determination of toxic doses in the whole animal, mainly in the cat, rather than from observations of the action of these compounds in isolated hearts. It follows as a natural consequence that the compounds with a rather weak toxicity have been condemned to be inactive, even if they have a strong cardiotonic action, in spite of the fact that such a kind of compounds may actually be more important from the clinical point of view. For example, the compound like dihydrodigitoxin of which the lactone ring is saturated, and the compound like resibufogenin, which have an epoxide ring between C14 and C15 instead of C14-OH, generally believed to be inactive based on the toxicity data in the cat, have recently been found to be fairly active when tested in the isolated heart (2-3). The authors also found that, different from the above-cited opinion, the presence of 3β-OH is not indispensable for the cardiotonic action of the cardenolides ; 3-epi-digitoxigenin was found to have a definite cardiotonic action upon the isolated frog's heart (See Fig. 8). These findings seem to warrant reexamination of the problem, on the basis of the action of these compounds in the isolated heart.
In recent years several adrenocortical steroids and aldosterone antagonists have been reported to be cardiotonic (4-6), despite the fact that their stereochemical structures are essentially different from those of the cardiotonic steroids. In view of these, the authors took up the problem of the cis-fusion of the C and D rings out of the several important points in the structure of cardiotonic steroids as discussed above and reexamined its importance for the specific cardiotonic action using the isolated frog's heart and the heart-lung preparation of the dog.View full abstractDownload PDF (332K) -
HIROSHI MURASE1965 Volume 15 Issue 1 Pages 72-81
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSMany years ago Katagi (1) and Freund (2) reported that some cardiotonic steroids and their glycosides could induce a sustained contracture in such skeletal muscle rich in slow muscle fibres as rectus abdominis muscle or gastrocnemius muscle of the frog after a rather long latent period. However, any due attention was not paid to this finding until very recently, when the same phenomenon was re-observed in this laboratory (3). Further study of this phenomenon in this laboratory (4) revealed one and the same structural requirements for both the contracture-inducing action and the cardiotonic action of these compounds, although it was demonstrated that this contracture was of nervous origin, somehow mediated by acetylcholine.
In order to test the possibility whether this phenomenon can be used as an assay method for the cardiotonic action of the cardenolides and bufadienolides, the relative potencies of the eight representative cardiotonic steroids were determined, using the length of the latent period of these compounds to produce contracture in the frog rectus abdominis muscle as a measure of their contracture-inducing activity, and was compared with the relative potencies of these compounds to produce cardiotonic action.View full abstractDownload PDF (349K) -
HIDEYO OSHIKA, KENGO NAKAI1965 Volume 15 Issue 1 Pages 82-87
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSAccumulating evidence indicates that monoamine oxidase (MAO, 1.4.3.4) is essential to the metabolism of serotonin and catecholamines. Since these amines are substances of high biological activity and have been implicated in autonomic function, it becomes of great interest to see whether foetal or embryonic development is closely related to the metabolism of these biogenic amines.
Therefore, evaluation of action of MAO inhibitor on animals in undeveloped stage may afford some clue as to the biological significance of the amines.
The present paper deals with appearance of MAO in the larval stage of the amphibian and also with effect of MAO inhibitor on the developmental mechanism.View full abstractDownload PDF (507K) -
RYOHEI IIDA, SACHIKO NAGATA, MORIO KAKIMOTO, HIROAKI AKAIKE, HIROKO WA ...1965 Volume 15 Issue 1 Pages 88-90
Published: March 01, 1965
Released on J-STAGE: February 02, 2007
JOURNAL FREE ACCESSDownload PDF (92K)
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