• 생명과학회지
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• 제13권5호
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• pp.634-641
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• 2003

외부에서 가해진 비소 스트레스가 내피유무에 따른 흰쥐 대동맥의 수축력 증가와 이완반응에 미치는 영향을 알아보고자 본 실험을 실시하였다. 혈압의 측정은 생리기록계를 이용하였고, 내피 유무에 따른 혈관의 수축력은 Organ bath에 조직을 걸고 자동조절 생리기록계를 이용하여 측정하였다. 중추신경계를 파괴시킨 흰쥐의 생체 내 실험에서 비소처리로 vasopressin과 phenylephrine에 의한 혈관 수축력은 대조군에 비해 각각 19.1%와 46.6%로 대동맥의 혈압은 상승되었다. 0, 0.5, 1, 2 및 4 mM As을 처리한 적출 대동맥 실험에서 phenylephrine $(10^{-6}M)$을 가했을 때 5시간까지는 혈관 수축력의 변화가 미미했으나 8시간째 비소 처리군은 대조군에 비해 39% 증가된 값을 보여 수축력이 더욱 유의하게 증가되었다. 내피 제거 시 저농도 비소처리에서 다소 신속한 수축반응을 보였으나 고농도 비소 처리시에는 내피유무에 따른 차이가 유의적이지 않았다. 이완제 sodium nitroprusside와 acetylcoline를 처리했을 때 대조군에 비해 다소 증가된 이완력을 보였고, 시간경과에 따라 내피 비의존적인 nitroprusside와 달리 내피 의존적인 acetylcholine에서 이완력이 대조군에 비해 다소 촉진되었다. 이상의 결과에서 4 mM As처리시 혈관의 수축력은 증가되었으나 내피유무에 따른 차이는 유의적이지 않았고, 내피가 혈관의 이완력을 다소 촉진시킨 것으로 나타났다. 결론적으로 비소처리한 혈관은 내피유무와 무관하게 수축력이 증가되어 장기간 고농도 비소에 노출 시 고혈압을 유발할 우려가 있을 것으로 여겨진다.

• The Korean Journal of Physiology and Pharmacology
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• 제21권4호
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• pp.385-395
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• 2017

Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline ($10^{-6}M$ and especially $10^{-7}M$) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations ($10^{-4}M$ and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor $N^w$-nitro-L-arginine methyl ester (L-NAME; $10^{-4}M$) or NO scavanger $OHB_{12}$ ($10^{-3}M$), as well as non-specific inhibition of $K^+$-channels with tetraethylammonium (TEA; $10^{-3}M$), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin ($10^{-5}M$) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at $3{\times}10^{-7}$ and $10^{-6}M$, but not at the highest concentration ($10^{-4}M$). Neither the 5-$HT_{1D}$-receptor selective antagonist BRL 15572 ($10^{-6}M$) nor 5-$HT_7$ receptor selective antagonist SB 269970 ($10^{-6}M$) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and $K^+$-channels and activation of some methiothepin-sensitive receptors, possibly of the 5-$HT_{2B}$ subtype.

• 동의생리병리학회지
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• 제22권6호
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• pp.1518-1524
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• 2008

Ponciri Fructus (PF), the immature fruit of Poncirus trifoliata, has been used for treatment of constipation in Korean traditional medicine. It has been reported that PF has a prokinetic effect on gastrointestinal tract, but little is known about the effect on colonic contraction. The aim of this study was to investigate the effect of PF on spontaneous contractions of proximal and distal colon in rats. The aqueous extract of PF was centrifuged and filtered and its supernatant was used for in vitro motility study. The removed colon from rats was divided into proximal and distal segments. Each segment was mounted in a 10 ml organ bath and measured the change of the spontaneous contraction with increasing dose (1, 5, 10, 50, 100, 500, $1000{\mu}g/ml$) of PF extract administration. Also the effect of PF on the spontaneous contraction was measured under treatment of atropine, acetylcholine (Ach), and tetrodotoxin (TTX). PF increased the spontaneous phasic contraction of distal colon dose dependently, but there was no change in proximal colon. The contractile response induced by PF in distal colon was lower than that of Ach and was partially blocked by atropine ($10^{-6}M$). TTX increased the spontaneous contraction and it was reinforced with Ach addition. But the extract of PF had no or little contractile effect of TTX in colon. PF increased spontaneous contractions selectively in distal colon. The prokinetic effect of PF may be due to enhancement of cholinergic related excitatory neural system.

• 약학회지
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• 제43권2호
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• pp.237-250
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• 1999

In order to investigate the pharmacologic properties of New Wonbang Woohwangchungsimwon Pill(NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10-6 M) regardless 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 relaxing effects of NSCH and SCH. NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCH and SCH decreased significantly heart rate. These, at high doses, had a negative inotropic effects 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 guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA), $V_{max}$ and resting membrane potential (RMP) at low doses, whereas inhibitory the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.

• 대한약리학회지
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• 제26권2호
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• pp.121-126
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• 1990

Lidocaine의 심근 수축력 억제작용의 기전을 규명하기 위한 일환으로 정상 Krebs-Ringer bicarbonate glucose용액에서 각종 대사기질이 lidocaine 억제심방과 정상심방의 수축력에 미치는 영향, 그리고 glucose 제거용액에서 lidocaine의 심방 수축력에 대한 영향을 검토하여 다음과 같은 결과를 얻었다. 1. Pyruvate(5mM), acetate(5mM), fructose(30mM)는 lidocaine에 의해 감소된 심방 수축력을 현저히 증가시켰으나, 정상심장에는 별 영향이 없었다. 2. Glucose(20mM)는 lidocaine억제심방의 수축력을 증가시키지 못하였으나 정상심방의 수축력을 현저히 증가시켰다. 3. Glucose 제거용액에서 lidocaine은 정상용액에서보다 심방 수축력을 현저히 더 감소시켰다. 이상의 결과로 보아 lidocaine은 적출심장에서 외인성 glucose를 제거시, 심장 glycogen의 이용을 glucose phosphate isomerase 단계 혹은 glycogen이 glucose-6-phosphates로 전환되는 단계를 억제한다는 것을 시사하고 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.253-261
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• 2000

Head-out water immersion induces marked increase in the cardiac stroke volume. The present study was undertaken to characterize the stroke volume change by analyzing the aortic blood flow and left ventricular systolic time intervals. Ten men rested on a siting position in the air and in the water at $34.5^{circ}C$ for 30 min each. Their stroke volume, heart rate, ventricular systolic time intervals, and aortic blood flow indices were assessed by impedance cardiography. During immersion, the stroke volume increased 56%, with a slight (4%) decrease in heart rate, thus cardiac output increased ${\sim}50%.$ The slight increase in R-R interval was due to an equivalent increase in the systolic and diastolic time intervals. The ventricular ejection time was 20% increased, and this was mainly due to a decrease in pre-ejection period (28%). The mean arterial pressure increased 5 mmHg, indicating that the cardiac afterload was slightly elevated by immersion. The left ventricular end-diastolic volume index increased 24%, indicating that the cardiac preload was markedly elevated during immersion. The mean velocity and the indices of peak velocity and peak acceleration of aortic blood flow were all increased by ${\sim}30%,$ indicating that the left ventricular contractile force was enhanced by immersion. These results suggest that the increase in stroke volume during immersion is characterized by an increase in ventricular ejection time and aortic blood flow velocity, which may be primarily attributed to the increased cardiac preload and the muscle length-dependent increase in myocardial contractile force.

• Natural Product Sciences
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• 제5권1호
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• pp.25-32
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• 1999

The pharmacological actions of ambrein were investigated alone or in combination as a pretreatment with agonists (adrenaline, noradrenaline, acetylcholine, histamine, nicotine), antagonists (atropine, atenolol) and calcium channel blocker (verapamil) in vivo in anaesthetized SWR rats using blood pressure, heart rate and myocardial contractility as parameters. Ambrein in the dose range of 50-200 mg/kg to the normotensive anaesthetized rats demonstrated negative chronotropic effect and increased the myocardial contractility significantly. At the mid dose (100 mg/kg) this increase in contractile force was 36% and 44% above the normal at 30 min and 60 min intervals post-treatment, respectively. Both of the lower and high doses (50 mg/kg and 200 mg/kg) had similar effects. Furthermore, this contractile response was dose related. Also, this compound produced a considerable increase in myocardial contractility when used as a pretreatment with some agonists and antagonists. The results on blood pressure did not show a considerable change when ambrein was used alone. However, ambrein pretreatment at the dose of 100 mg/kg did not block the effects of adrenaline, noradrenaline, isoprenaline and acetylcholine on heart rate and blood pressure. On the other hand, this pretreatment attenuated the sympathoadrenal effects of nicotine significantly. Chronotropic and blood pressure changes produced by histamine were also inhibited by ambrein pretreatment. This pretreatment significantly reversed the effects of atenolol but failed to demonstrate any change in the negative chronotropic, inotropic and hypotensive responses induced by verapamil. It is concluded that ambrein induced nonselective dose dependent antagonism of the effects of some agonists and antagonists require contribution of some neuromediators. However, the positive isotropic effects of ambrein possibly involve the enhancement of slow Ca channels and/or activation of ${\beta}-adrenergic$ receptors in the heart. At this moment it is difficult to explain the exact mode of action of ambrein and the studies dealing with Ca channel blocker and adrenergic blocker followed by ambrein may help to define the factors which contribute to its positive inotropic effects.

• 대한한의학회지
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• 제19권2호
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• pp.228-243
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• 1998

This study was undertaken to evaluate the effect of Sunghyangchungisan (SHCS) on the regulation of vascular tone. Vascular rings isolated from rabbit carotid artery were myographed isometrically in isolated organ baths and the effect of SHCS on contractile activities were determined. SHCS relaxed the arterial rings which were pre-contracted by phenylephrine(PE). The responses to SHCS were partially dose-dependent at concentrations lower than 0.5 mg/ml. When SHCS was applied prior to the exposure to PE, it inhibited the PE-induced contraction by a similar magnitude which was comparable to the relaxation of pre-contracted arterial rings. Washout of SHCS after observing its relaxant effect resulted in a full recovery of PE-induced contractions, indicating that the action mechanism is reversible. The observation that SHCS did not change the $ED_{50}$ of PE on its dose-response curve ruled out the possible interaction of SHCS and ${\alpha}-receptor$. The relaxant effect of SHCS was not affected by removal of endothelium, and pretreatment of the arterial rings with methylene blue or nitro-L-arginine. This results suggest that the action of SHCS is not mediated by endothelium nor soluble guanylate cyclase. SHCS relaxed high $K^{+}-induced$ contractions as well, whereas it failed to relax phorbol ester-induced contractions. When contraction was induced by additive application of $Ca^{2+}$ in arterial rings which were pre-depolarized by high $K^+$ in a $Ca^{2+}-free$ solution, the relaxant effect of SHCS was attenuated by increasing the $Ca^{2+}$ concentration. SHCS, when applied to the arterial rings pre-contracted by PE and then relaxed by nifedipine, a $Ca^{2+}$ channel blocker, did not show additive relaxation. From above results, it is suggested that SHCS relax PE-induced contraction of rabbit carotid artery in an endothelium-independent manner, and inhibition of $Ca^{2+}$ influx may contribute to the underling mechanism.

• 대한본초학회지
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• 제22권2호
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• pp.25-33
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• 2007

Objectives : Oriental pear was used as treatment of asthma, control of blood pressure, diabetes in oriental medicine. The aim of this study was to observe the effects of Phenolic compound extracted from pear and herbal drugs to treat asthma. Methods : In order to study the effect of oral administration of phenolic compound extracted from pear and herbal drugs(Platycodon grandiflorum, Prunus armeniaca) on allergic asthma, mice were pre-treated by oral administration of the solution before antigen sensitization four times for 8 days. 2 days later, mice were actively sensitized with a subcutaneous injection of ovalbumin and 13 days later, they were provoked with ovalbumin aerosols. The animals were divided into four groups; Saline, orally administered saline. PC-A, orally administered Phenolic compound extracted from pear peel 10mg/kg/ml. PC-B, orally administered Phenolic compound extracted from pear peel and flesh 10mg/kg/ml. PC-C, orally administered pear 10m/kg/ml, Platycodon grandiflorum 24.4 mg/kg/ml and Prunus armeniaca 33.3 mg/kg/ml. Serum level of IgE, IL-4, cell numbers in the bronchoalveolar lavage fluid(BALF), and in vitro isometric contractile responses of the isolated tracheal smooth muscle(TSM) to acetylcholine(ACh, $0.1-1000{\mu}M$), KCl were measured. Results : Contractile responses of TSM to ACh were decreased in PC-A group at Ach 0.1, 0.3, 1 ${\mu}M$, decreased in PC-B at 0.1 ${\mu}M$ and decreased in PC-C at 0.1, 0.3, 1, 10, 30 ${\mu}M$. The maximal contractile response of TSM to KCl was decreased in PC-C group, The cell numbers of eosinophil in BALF were decreased in PC-C group, and those of macrophages in BALF were decreased in PC-A and PC-C group. Interleukin-4 in BALF was decreased in PC-A, PC-B, PC-C group. Conclusion : Based on the above results it is assumed that oral administration of phenolic compound extracted from pear and herbal drugs can help the treatment of deficiency allergic Asthma.

• 대한한방내과학회지
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• 제21권3호
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• pp.377-388
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• 2000

Objective : This study was undertaken to evaluate the effect of Sunghyangchungisan (SHCS) on the regulation of vascular tone and $Ca^{2+}$ metabolism in arterial tissues. Vascular rings isolated from rabbit carotid artery were myographed isometrically in isolated organ baths and the effect of SHCS on contractile activities, endothelial function and $Ca^{2+}$ metabolism were determined. Methods : In phentobarbital sodium-anesthetized rabbits, SHCS administered through ear vein (100 mg/Kg body wt.) or intragastric dwelling tube (300 mg/Kg body wt.) attenuated phenylephrine (PE, 10 ${\mu}g$/Kg, i.v.)-induced increases in both systolic and diastolic cartoid arterial blood pressure. Results : In experiments with isolated arterial strips, SHCS relaxed arterial rings which were pre-contracted by phenylephrine (PE, 1 ${\mu}M$). The responses to SHCS were partially dose-dependent at concentrations lower than 0.5 mg/ml. When SHCS was applied prior to the exposure to PE, it inhibited the PE-induced contraction by a similar magnitude which was comparable to the relaxation of pre-contracted arterial rings. Washout of SHCS after observing its relaxant effect resulted in a full recovery of PE-induced contractions, indicating that the action mechanism is reversible. The observation that SHCS did not change the $ED_{50)$ of PE oh its dose-response curve ruled out the possible interaction of SHCS with ${\alpha}$-receptors. The relaxant effect of SHCS was not affected by removal of endothelium or a nitric oxide synthase inhibitor, L-NAME. Methylene blue, an inhibitor of the soluble guanylate cyclase, did not affect the relaxant effect of SHCS. These results suggest that the action of SHCS is not mediated by the endothelium nor soluble guanylate cyclase. Constant cGMP production determined in arterial strips in the presence or absence of SHCS is consistent with this conclusion. When contraction was induced by additive application of $Ca^{2+}$ in arterial rings which were pre-depolarized by high $K^+$ in a $Ca^{2+}$-free solution, the relaxant effect of SHCS was attenuated by increasing the $Ca^{2+}$ concentration. SHCS, when applied to the arterial rings pre-contracted by PE and then relaxed by nifedipine, a $Ca^{2+}$ channel blocker, did not show additive relaxation. SHCS partially blocked $Ca^{2+}$ influx stimulated by PE and high $K^+$ which was determined by 5-min ^{45}Ca$ uptake, while it did not affect $Ca^{2+}$ efflux. Conclusions : From above results, it is suggested that SHCS relax PE-induced contraction of rabbit carotid artery in an endothelium independent manner, andinhibition of $Ca^{2+}$ influx may contribute to the underling mechanism.