• Biomolecules & Therapeutics
• /
• 제5권4호
• /
• pp.390-401
• /
• 1997

In order to investigate the pharmacological properties of New Woohwangchungsimwon Liquid (NCL), effects of Woohwangchungsimwon Liquid (CL) and NCL were compared. In isolated rat aorta, NCL and CL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) without regard to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxation of NCL and CL. NCL and CL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NCL and CL significantly decreased heart rate. NCL and CL, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NCL and CL had no effects on parameters of action potential at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NCL and CL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between two preparations.

• Biomolecules & Therapeutics
• /
• 제7권1호
• /
• pp.66-78
• /
• 1999

In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD$_{90}$ and V$_{max}$ at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.s.

• 약학회지
• /
• 제28권5호
• /
• pp.257-263
• /
• 1984

In our former report we observed that cinnarizine influenced the antihypertensive effect of propranolol beneficially, but not of metoprolol in SHR and normal cat. Cardiac contractilities and smooth muscle relaxations induced by above drugs were measured to elucidate their mechanism of action. In cinnarizine and propranolol treated group, both of negative inotropic and ${\beta}-blocking$ activity of propranolol in perfused rat hearts were increased and propranolol induced contraction in isolated arterial and trachea smooth muscle of the guinea pig was antagonized comparing to propranolol alone treated group. However, in the cinnarizine and metoprolol treated group, no significant differences in activity on the above were observed compared to metoprolol alone treated group.

• The Korean Journal of Physiology
• /
• 제23권2호
• /
• pp.225-236
• /
• 1989

1) At the isolated perfused guinea-pig and rat heart heterometric autoregulation of the myocardium and myogenic autoregulation of the coronary vessels were induced by means of stepwise increases of perfusion pressure. 2) According to this loading test Frank-Starling function curves of the left ventricle and pressure-flow curves of the coronary vessels can be drawn. This graphic evaluation gives more information about the condition of the heart and the coronary vessels than simple evaluation under hemodynamic equilibrium. 3) There are significant differences in both curves between animal species and between different perfusate Mg concentration. 4) Myogenic autoregulation is not affected by the cyclooxygenase inhibitors indometacin and me- clofenamate. Thus it appears unlikely that prostanoides are involved in myogenic autoregulation. 5) Ca antagonists (Gallopamil, prenylamine) depress myogenic autoregulation dose-dependently. Enhanced myogenic autoregulation, induced by low extracellular magnesium, can be reduced effectively by Gallopamil. 6) Ginsenosides from Panax ginseng as well as the ginsenoside 'Rg' are effective inhibitors of myogenic autoregulation without major negative inotropic effects.

• 대한약리학회지
• /
• 제10권1호
• /
• pp.55-59
• /
• 1974

Further elucidation of the mechanism of halothane's negative inotropic action has resulted from a study of the effect of various substrates on halothane-depressed rat atria. Approximately 6 mg% halothane was required to maintain a 50% depression of the contractility of rat atria suspended in a modified Krebs-Ringer bicarbonate glucose medium, pH 7.4, $30^{\circ}C$ for 2hr. Both lactate and acetate were found to restore partially the contractility of halothane-depressed atria. The maximally effective concentration of lactate was 5 mM; for acetate it was 2.5mM. Neither 5 nor 20 mM of additional glucose was effective in restoring the force of contraction of halothane-depressed atria. The results are consistent with the hypothesis that halothane exerts at least a part of its negative inotropic effect on rat atria by inhibiting either the uptake or utilization of glucose by the myocardium. The site of blockade must be prior to the conversion of pyruvate to acetyl CoA. In our previous report dealing with the mechanism of cardiac depressant action of inhalation anesthetic halothane, it has been demonstrated that: 1) approximately 6 mg/100 ml halothane is required to maintain 50% depression of the force of contraction of isolated rat atria in Krebs-Ringer bicarbonate glucose medium; 2) pyruvate partially restores the contractility of halothane-depressed atria, but has no effect on normal atria; the partial recovery of depressed atria by the addition of sodium pyruvate is due to the effect of the pyruvate ion itself, not to the sodium ion; 4) addition of pyruvate, to atria depressed with hypertonic medium, produced only further depression. From these findings we concluded that the cardiac depressant action of halothane on rat atria is a manifestation of inhibition of glucose uptake or utilization. The present studies were undertaken to observe the effect of other substrates on halothane-depressed atria in order to substantiate our conclusion. As with the case of pyruvate, lactate and acetate also partially restored the force of contraction of halothane-depressed atria. These data are consistent with the hypothesis that halothane inhibits glucose uptake or utilization in the glycolytic cycle of the myocardium.

• 약학회지
• /
• 제41권6호
• /
• pp.802-816
• /
• 1997

In order to investigate the pharmacological properties of New Woohwangehungsimwon Pill (NWCH). Effects of Woohwangehungsimwon Pill (WCH) and NWCH were compared using various experimental models. In isolated rat aorta, NWCH and WCH showed the relaxation of blood vessels in maximum contractile response to phenylephrine ($10^{-6}$M) without regard to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxative effects of NWCH and WCH. NWCH and WCH inhibited the vascular contractions induced by acethylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats(SHRs), NWCH and WCH decreased significantly heart rate. These, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, these had no effects on parameters of action potential at low doses, whereas inhibited the cardiac, contractility at high doses. Furthermore, these had a significant inhibitory effects on heart acceleration in normotensive rats and SHRs. These results suggested that NWCH and WCH have weak cardiovascular effects, and that there is no significant differences between two preparations.

• Journal of Chest Surgery
• /
• 제19권2호
• /
• pp.197-208
• /
• 1986

Propranolol is one of clinically useful antiarrhythmic agents and electrophysiologically classified as group II. And the negative inotropic effect which is not related to adrenolytic effect has been demonstrated with high concentration of propranolol. On the other hand, it has been well known that the calcium plays a central role in excitation-contraction coupling process of myocardium and also in electrophysiological changes of cell membrane. Author studies the effect of propranolol on calcium uptake and release in sarcoplasmic reticulum and mitochondria prepared from porcine myocardium to investigate the mechanism of action of propranolol on myocardium. The results are summarized as follow: 1] The maximum Ca++-uptake of sarcoplasmic reticulum is inhibited by propranolol in a dose dependent manner. 2] The release of calcium from sarcoplasmic reticulum is not affected by propranolol but with higher than 1x10-3 M of propranolol, rate of calcium release from sarcoplasmic reticulum is decreased. 3] Propranolol inhibits the maximum uptake and uptake rate of calcium in mitochondria non-competitively. [Ki = 6.21 x 10-4 M] 4] The rate of Na+ induced calcium release from mitochondrion shows a function of [Na+]2 and is inhibited by propranolol with the concentration significantly lower than that affect the calcium uptake in sarcoplasmic reticulum and in mitochondria [Ki = 2.91 x 10-5 M]. These results suggest that propranolol affects the intracellular calcium homeostasis which may considered to be one of the mechanism of action of propranolol on myocardium.

• 대한약리학회지
• /
• 제10권1호
• /
• pp.21-39
• /
• 1974

Certain metabolic aspects of halothane's cardiac depressant action on the contractility of the myocardium were elucidated from a sudy of the effect of pyruvate on halothane-depressed rat atria. Approximately 6 mg% halothane was required to maintain a 50% depression of the contractility of rat atria suspended in a modified Krebs-Ringer bicarbonate glucose medium, pH 7.4, $30^{\circ}C$ for a 2 hr. period. Pyruvate was found to restore partially the contractility of halothane-depressed atria. The maximally effective concentration of pyruvate was 2.5 mM. There was minimal pyruvate effect on the force of contraction of control atria. The effect of pyruvate on halothane-depressed atria was shown to be due to the pyruvate and not the sodium ion of the sodium pyruvate. Pyruvate was found to produce no increase in the contractility of atria depressed by hypertonic medium, but caused a further depression. Selected aspects regarding the action of halothane on glucose metabolism in myocardial cells are discussed. The results are consistent with the hypothesis that at least a part of the negative inotropic action of halothane is due to an inhibition of glucose uptake or utilization in the glycolytic pathway.

• The Korean Journal of Physiology
• /
• 제7권2호
• /
• pp.31-37
• /
• 1973

The effects of ethanol extacts of aconite root (Aconitum koreanum) on mean arterial pressure, heart rate, pulse pressure, and respiration were investigated and also studied the effect on electrical activation of the hypothalamus in cats. From the present experiment the following results were obtained. 1) On administering 5 mg or 10 mg aconite extracts per kg of body weight, the mean arterial blood pressure declined markedly possibly as the result of negative inotropic and chronotropic effects of aconite. 2) From the enhanced pressor responses to intravenously injected epinephrine, the existance of vasodilatory effect of the aconite was suggested. 3) After administration of aconite extract, no significant differences were observed in the presser responses to carotid occlusion and to electrical stimulation of the hypothalamus. It is, therefore, concluded that the aconite extract exerts no significant effect on the excitability of hypothalamus as well as medullary cardiovascular center of cats. 4) After administration of $5{\sim}10$ mg/kg aconite extracts, respiratory rate was increased while depth of respiration decreased. On the otherhand, respiratory rate was markedly decreased by injection of 20 mg/kg aconite into animal.

• 대한약리학회지
• /
• 제28권1호
• /
• pp.41-48
• /
• 1992

국소마취제인 bupivacaine의 심근억제작용에 관한 기전을 규명하기 위하여, bupivacaine에 의해 수축력이 감소된 흰쥐 적출심장에 대한 각종 대사기질의 영향을 관찰한 바 다음과 같은 결과를 얻었다. 1. Krebs-Ringer glucose medium에 현수한 적출심방의 수축력은 0.01% bupivacaine에 의해 약 50% 감소되었다. 2. Pyruvate, acetate 및 fructose는 bupivacaine 억제심방의 수축력을 증가시켰으나, 정상 Krebs-Ringer medium에서의 수축력에는 현저한 영향이 없었다. 3. Glucose는 bupivacaine 억제심방의 수축력에는 별 영향이 없었으나, 정상 Krebs-Ringer medium에서의 수축력은 증가시켰다. 4. Pyruvate, acetate 및 fructose는 hypertonic medium에 의해 억제된 심방의 수축력에 영향이 없었으나, glucose는 약간의 수축력 증가를 보였다. 5. 각종 대사기질중 pyruvate가 bupivacaine 억제심방의 수축력을 최대로 증가시켰다. 이상의 결과는 bupivacaine이 심근의 glucose 섭취를 억제하거나, 해당과정을 통한 glucose의 이용을 억제하였음을 시사한다. 나아가서, bupivacaine에 의한 대사억제는 심근의 해당과정에서의 phosphofructokinase step이전의 단계에서 작용함을 시사하고 있다.