• YAKHAK HOEJI
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• v.32 no.2
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• pp.129-136
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• 1988

Effects of the selective alpha-adrenoceptor agonists, clonidine, oxymetazoline and phenylephrine, on heart rate and contractile force were investigated in the isolated frog atria and it was attempted to examine the influence of adrenoceptor antagonist upon those. Clonidine produced dose-dependent negative chronotropic and positive inotropic effects. The negative chronotropic effect was significantly attenuated in the presence of prazosin and yohimbine but not propranolol. The positive inotropic effect was significantly attenuated by prazosin, yohimbine and propranolol. Oxymetazoline produced dose-dependent negative chronotropic and inotropic effects. The negative chronotropic effect was significantly attenuated in the presence of prazosin, which was partially augmented by yohimbine but was not affected by propranolol. The negative inotropic effect was not affected by propranolol but it was partially augmented by yohimbine and was partially attenuated by prazosin. Phenylephrine produced dose-dependent positive chronotropic and inotropic effects. The positive chronotropic and inotropic effect were significantly attenuated in the presence of propranolol but were not affected by prazosin and yohimbine. These results suggest that the negative chronotropic effect by clonidine and oxymetazoline is mediated by alpha-adrenoceptors, the positive chronotropic and inotropic effects by phenylephrine are mediated by beta-adrenoceptors, and alpha-adrenoceptors mediated the inhibitory chronotropic responses exists in the isolated frog atria.

• YAKHAK HOEJI
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• v.24 no.1
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• pp.15-25
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• 1980

The investigation is concerned with the action of ginseng saponin on the contractile force in the rat heart and with the elucidation of the mechanism of the action. The effect of total ginseng saponin, ginsenoside Rb$_{1}$ of protopanaxadiol derivatives and ginsenoside Re of protopanaxatriol derivatives on the contractile force in isolated spontaneously beating normal rat heart was investigated. Total ginseng saponin was obtained from white ginseng by the method of Shibata and Namba. Ginsenoside Rb$_{1}$ and ginsenoside Re were isolated by the method of and Han, respectively. Total ginseng saponin exhibited a slight increase of the contractile force. Ginsenoside Rb$_{1}$ increased markedly the contractile force and dose dependent increase in contractile force was observed. However, ginsenoside Re did not increase the contractile force, but it prevented spontaneous decrease of the contractility of the heart. The mixture of the same dose of ginsenoside Rb$_{1}$ and Re showed a slight increase in the contractile force and its effect was similar to that obtained by total ginseng saponin. Pretreatment with propranolol abolished the positive inotropic effect of ginsenoside Rb$_{1}$ and the positive inotropic effect of ginsenoside Rb$_{1}$ was not observed in a reserpinized rat heart. Pretreatment with ginsenoside Re decreased or abolished the positive inotropic effect of epinephrine. Activities of Na+, K+ -ATPase were inhibited by ginsenoside Rb$_{1}$, total ginseng saponin and ginsenoside Re and these inhibitory effects were dose dependent. The results suggest that catecholamine release or inhibition of Na+, K+ -ATPase activities may be involved in the positive inotropic effect of gindenoside Rb$_{1}$. Ginsenoside Re counteracted the positive inotropic effect of ginsenoside Rb$_{1}$.

• The Korean Journal of Physiology
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• v.20 no.2
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• pp.175-183
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• 1986

Since it was proposed that vanadate may be an ‘ideal endogenous regulator of the $Na^+,\;K^+-ATPase$ activity (Cantley et at, 1979), vanadate has been a subject of intensive research and a variety of its physiological effects have been described (Nechay, 1984). In isolated guinea pig heart muscle vanadate shows a positive inotropic effect on ventricular muscle, while it induces a negative inotropic effect on atrial muscle. But its underlying mechanism has not been elucidated so far. Therefore, in this study the flux rates of calcium ion into and from guinea pig heart muscle were measured to throw some light on the underlying mechanism, because those rates have been known to be closely related to the cardiac contractility and the results are summarized as follows: 1) Calcium efflux rates from the intracellular $Ca^{++}$ pool (compartment 4) of both guinea pig left atrium and right ventricle were significantly reduced by vanadate and their pool sizes were significantly increased by vanadate. 2) The magnitude of calcium influx into left atrium was reduced by vanadate, While the magnitude of calcium influx into right ventricle was not affected by vanadate. From these results, it may be concluded that the positive inotropic effect of vanadate on the ventricular muscle was due to a reduced efflux rate of calcium ion and its negative inotropic effect on atrial muscle was resulted from a reduced influx of calcium ion.

• The Korean Journal of Pharmacology
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• v.17 no.1 s.28
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• pp.9-15
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• 1981

Aconiti tuber butanol fraction, which is isolated from the chloroform insoluble and water soluble extract of Aconitum volubile, has been recently known to have a potent positive inotropic effect in the isolated cardiac muscle preparations of various animals. The positive inotropic mechanism of Aconiti tuber butanol fraction, in relation with the external calcium, was studied using the isolated cat papillary muscle. The positive inotropic effect was dependent on the calcium concentration in the nutrient medium, and a synergistic relation could be demonstrated between Aconiti tuber butanol fraction and the external calcium. The inotropic effect of $10^{-4}g/ml$ of Aconiti tuber butanol fraction was equivalent to that of 0.06mM of calcium in the medium. After the treatment with a calcium influx inhibitor, Verapamil$(2{\pm}10^{-7}-10^{-6}M)$, the contractile force of the papillary muscle was markedly inhibited. In these preparations, Aconiti tuber butanol fraction restored the decreased contractility in a dose-dependent manner. It was suggested that the positive inotropic effect of Aconiti tuber butanol fraction might be related with the stimulating action on the calcium influx through the slow inward calcium channels in the cardiac cell membrane. In contrast with digitalis cardiac glycoside, Aconiti tuber butanol fraction infused intravenously into the anesthetized rabbit decreased the systemic arterial blood pressure and increased the carotid blood flow, but produced no prominent changes in the heart rate.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.1
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• pp.40-46
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• 2016

Many medicinal plants have been used for the treatment of edema, jaundice, and gonorrhea in traditional Oriental medicine. This screening study was designed to search the positive inotropic effects of herbal extracts in beating rabbit atria. Aquarius extracts of twenty six herbs were examined in atrial mechanical dynamics such as pulse pressure and stroke volume and atrial natriuretic peptide (ANP), one of the main hormones involved in the regulation of the body fluid and blood pressure homeostasis in perfused beating rabbit atria. Sophora flavescens Ait., Rheum officinale Baill., Acorus gramineus Sol., Chelidonium majus L., Pulsatilla koreana Nakai., Reynoutria japonica Houtt., Euphorbia lathyris L., Pyrrosia lingua (Thunb.) Farwell, Poncirus trifoliata Rafin., Anemarrhena asphodeloides Bunge, Kochia scoparia Schrad. significantly increased stroke volume and pulse pressure. However, those herbal extracts were not induced ANP secretion. We clarified the eleven herbal extracts for the positive inotropic effect independent of ANP secretion in beating rabbit atria. Thus these results provide a beneficial data for the treatment of the impairment of body fluid and blood pressure in traditional Oriental medicine.

• The Korean Journal of Pharmacology
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• v.19 no.2
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• pp.9-16
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• 1983

The effect of higenamine upon the interval-strength relationship was kinetically analyzed, and compared them with epinephrine and calcium ion. The followings are result obtained : 1) Polyphasic patterns were seen by all agents applied on the interval-force curve of rabbit atrial muscle. 2) Higenamine, unlike calcium ion, increased the amount of PIEA produced per beat dose-dependently and scarcely affected the disappearance of NIEA. 3) Higenamine appeared to similar pattern with epinephrine in augmenting the PIEA, not affecting the NIEA. 4) Calcium ion slightly influenced the PIEA, rather hastened the disappearance of NIEA. From these result the positive inotropic action of higenamine was attributed solely to increment of PIEA.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.7-16
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• 1981

Higenamine ($Ca_{26}H_{17}No_3$. HCI, d1-1- (4-hydroxybenzyl) -6,7-dihydroxy-1,2,3,4-tetrahydroiso-quinoline hydrochloride), which has recently teen isolated from the Aconite root, was known to the cardiotonic component of the Aconite root. The positive inotropic effect of Higenamine was observed in the isolated electrically driven left atrium from rabbits with respect to the influences of extracellular calcium and of calcium antagonists, e.g. $La^{+++}$ and verapamil. A synergistic relation in the positive inotropic effect could be demonstrated between Higenamine and extra cellular calcium. The inotropic potency of $10^{-7}\;g/ml$ Higenamine was equivalant to that of 0.058 mM of calcium in the medium. In the preparation, of which contractility had been reduced by the treatment of $La^{+++}(10^{-5}-10^{-4}M)$ and verapamil$(2{\times}10^{-7}-10^{-6}M)$, Higenamine was able to restore the contractility. These results indicated that one of the possible mechanism of positive inotropism of Higenamine was to accelerate the influx of calcium from the extracellular space through the sarcolemma.

• The Korean Journal of Pharmacology
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• v.2 no.1 s.2
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• pp.21-29
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• 1966

Dichloroisoproterenol(DCI) i; one of the well known ${\beta}$-adrenergic receptor blocking agents. According to Moran and Perkins, DCI has sympathomimetic like action in relatively low concentrations. Fleming and Hawkins confirmed that DCI acts upon the receptors concerned with positive chronotropic and inotropic actions in the heart. Vogins reported that DCI, in concentration of $5{\times}10^{-8}$ to $5{\times}10^{-6}g/ml$, had properties of sympathomimetic amine causing positive inotropic and chronotropic actions in normal rat atria. And James and Nadeau found that DCI had not only adrenergic blocking effect in moderate and higher concentrations, but it also blocked the effect on the sinus node by vagal stimulation and of directly administered acetylcholine in higher concentrations. As stated above by many authors, DCI has complicated actions according to its concentrations. Our aim at the present experiments was to study the effects of DCI to the action of ouabain and acetylcholine upon the excised rabbit atria, as well as to the action of barium chloride and acetylcholine upon the excised rabbit intestine. In addition, Pan ax Ginseng is widely used as tonics in oriental nations, its pharmacological action, however, has not been clearly established. So we atempted to investigate the effects of the water extract of Panax Ginseng to the action of ouabain and DCI upon both atria and intestine. The results obtained were as follows. 1) DCI has a negative inotropic effect on the excised rabbit atria at concentration of $10^{-5}$ and a positive inotropic effect at concentration of $10^{-6}$. 2) DCI (at concentration of $10^{-6}$) potentiates the positive inotropic effect of ouabain upon the excised rabbit atria. 3) DCI antagonizes the action of acetylcholine upon the excised rabbit atria. 4) The water extract of Panax Ginseng, at concentration of $10^{-3}$, decreases the contractile force of rabbit atria, and tends to slightly increase that of rabbit atria at $10^{-4}$. 5) The water extract of Panax Ginseng exhibits a synergistic action with ouabain on the contractile force of rabbit atria. 6) DCI, in concentrations of $10^{-7}{\sim}10^{-6}$, depresses the tone and amplitude of contraction of the excised rabbit intestine. The depression of the intestinal tone markedly appears in pretreatment with reserpine 2mg/kg 24 hours. 7) DCI antagonizes the contractile effect of barium chloride on the excised rabbit atria. 8) DCI has no significant influence on the action of acetylcholine upon the excised rabbit intestine. 9) The series of those evidences indicates that DCI has a sympathomimetic-like action and more over a relaxing action directly on the excised rabbit intestine. 10) The water extract of Panax Ginseng in concentrations of $10^{-4}{\sim}10^{-3}$, has transient depression of the intestinal tone, but later gradually recovers its normal motility: 11) The water extract of Panax Ginseng has a synergistic action with ouabain on the intestinal contractility.

• YAKHAK HOEJI
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• v.18 no.3
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• pp.165-182
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• 1974

• YAKHAK HOEJI
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• v.55 no.2
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• pp.168-171
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• 2011

Chrysosplenol C [5,6-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxychromen-4-one] is a flavonoid found in Miliusa balansae and Pterocaulon sphacelatum. We have recently shown that chrysosplenol C has positive inotropic effect in isolated rat ventricular myocytes. In the present study, we explored a possible mechanism for the positive inotropic effect of chrysosplenol C by examining intracellular $Ca^{2+}$ transients during action potentials. The intracellular $Ca^{2+}$ transients were measured by confocal $Ca^{2+}$ imaging in field-stimulated single rat ventricular myocytes. Chrysosplenol C (50 ${\mu}M$) significantly increased the magnitudes (${\Delta}F/F_0$) of $Ca^{2+}$ transients (control, $1.08{\pm}0.05$; chrysosplenol C, $1.25{\pm}0.03$; n=8, P<0.01). Half decay time of the action potential-induced $Ca^{2+}$ transient was not altered by chrysosplenol C (50 ${\mu}M$) (control, $154{\pm}6$ ms; chrysosplenol C, $167{\pm}11$ ms; n=21). The $Ca^{2+}$ content in the sarcoplasmic reticulum (SR), measured as caffeine (10 mM)-induced $Ca^{2+}$ transient, was significantly decreased by chrysosplenol C (50 ${\mu}M$). These results indicate that chrysosplenol C increases $Ca^{2+}$ transients without altering $Ca^{2+}$ removal kinetics in ventricular myocytes, providing a possible mechanism for its positive inotropic effect.