• 약학회지
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• 제32권2호
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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.

• 약학회지
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• 제24권1호
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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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• 제20권2호
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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.

• 대한약리학회지
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• 제17권1호
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• pp.9-15
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• 1981

부자성분중 강심효과를 나타내는 부자부타놀분획의 작용기전을 심근수축기전이 있어서 중심적인 역활을 하는 칼슘이온과의 상호관계에서 검토하였으며 아울러 동물생체내 혈동력학에 대한 영향을 관찰하였다. 부자부타놀분획 적출 고양이 유두근표본의 수축력증가작용에 있어서 심근외칼슘과 상승적이었으며 부자부타놀분획 $10^{-4}g/ml$는 칼슘 0.06mM과 동등한 심근수측증강 효과를 나타내었다. 심근세포막의 칼슘통로 억제약물인 verapamil 존재하에서 저하된 유두근 수축력은 부자부타놀분획에 의하여 용량의존적으로 회복되었으며, 이로부터 부자부타놀분획의 강심작용기전의 일부는 심근세포막의 완만내향성 칼슘통로를 통한 칼슘유입을 측진하는 것과 관계가 있을 것으로 추측하였다. 정상가토의 혈동력학에 있어서 부자부타놀분획은 디지탈리스배당체와는 달리 용량의존적으로 전신동맥압을 저하시키고, 경동맥혈류량을 증가시켰으며, 심박동수에는 크게 의미있는 변화를 보이지 않았다.

• 동의생리병리학회지
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• 제30권1호
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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.

• 대한약리학회지
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• 제19권2호
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• pp.9-16
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• 1983

현재 사용되고 있는 강심제로는 디지탈리스 배당체가 유일한 약물이지란 그 안전역이 대단히 좁아서 보다 안전한 강심제의 개발이 요구되고 있다. 최근 강심작용이 현저할 뿐 아니라 안전역이 비교적 넓을 것으로 인정되는 higenamine이 개발되어 그 작용기전을 밝히려는 시도가 많이 있었다. 본 연구에서는 higenamine의 강심작용 기전을 규명하기 위한 연구의 일환으로 수축빈도-수축력 상관관계(interval-strength relationship)에 있어서 1) Rested-state수축력 2) Positive inotropic effect of activation(PIEA) 3) Negative inotropic effect of activation(NIEA)에 대한 higenamine의 영향을 $Ca^{++}$및 epinephrine과 비교 분석하였다. 실험결과 칼슘은 PIEA를 증가시키기 보다는 오히려 NIEA의 소멸을 촉진함으로써 강심작용을 나타내며 epinephrine 및 higenamine은 PIEA를 증가시키고 NIEA에는 거의 영향을 미치지 않았다.

• 대한약리학회지
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• 제17권2호
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• pp.7-16
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• 1981

심근 수축기전에 있어서 중심적인 역할을 하는 칼슘 이온과 Hienamine과의 상호작용을 비교 검토하였고 아울러 이 강심효과에 대하여 칼슘길항제인 란타눔과 verapamil을 사용하여 이에 미치는 영향을 관찰하였다. Higenamine은 적출 가토좌심방근에 대해 심근의 칼슘과 상호보완적인 상승 및 상가작용을 나타내었고 Higenamine $10^{-7}g/ml$은 0.058mM의 칼슘과 동등한 심근 수축증강효과를 나타내었으며 부자부타놀 분획물과 비교할 때 약 1,000배 정도 강력한 강심작용을 나타내었다. 또한 심근세포막의 칼슘유입을 억제한 조건인 란타눔과 verapamil처치시에도 Higenamine은 용량의존적으로 저하된 심근 수축력을 회복시킴으로 미루어 볼 때 Higenamine외 강심작용기전의 일부는 세포막을 통한 칼슘의 유입을 촉진시키는 것일 것으로 추측하였다.

• 대한약리학회지
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• 제2권1호
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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.

• 약학회지
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• 제18권3호
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• pp.165-182
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• 1974

• 약학회지
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• 제55권2호
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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.