• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.86-86
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• 1993

혈관근의 수축 또는 이완 반응에서 $Na^{＋}$/Ca$^{2＋}$ exchange계의 역할을 알아보고자 먼저 가토와 흰쥐 흉부 대동맥에서 수축과 이완 반응을 검색하고 이때의 혈관 이완 반응을 증개하는 cAMP와 cGMP농도를 측정하였다. 내피세포가 존재한 표본에서 acetylcholine은 norepinephrine 수축 반응을 이완시켰고 이완 반응은 methylene blue로 소실되었으며 isoproterenol과 nitroprusside는 내피 존재와 제거 양표본에서 이완 반응을 일으켰으며 이때 isoproterenol은 CAMP농도를, nitroprusside는 cGMP농도를 증가시켰다.

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.91-102
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• 1990

The effects of extracellular $Ca^{2+}$ and various $Ca^{2+}$ antagonists on endothelium-dependent relaxation to acetylcholine were studied in the isolated rabbit thoracic aorta in order to elucidate the control mechanism of endothelium derived relaxing factor (EDRF) release. Endothelium was removed from aortic strips by gentle rubbing with cotton ball. The effect of hemoglobin on basal tension was also observed with hemolysate. The results obtained were as follows: 1) Endothelium-dependent relaxation (EDR) to acetylcholine (ACh) showed biphasic pattern; the initial rapid relaxation phase and the late slow relaxation phase. 2) With the depletion of the extracellular $Ca^{2+}$, EDR was gradually suppressed, especially the late slow relaxation. 3) Verapamil, nifedipine, $Mn^{2+}$ and $Cd^{2+}$ had not any effect on EDR, while $La^{3+}$ and $Co^{2+}$ suppressed EDR completely. 4) The resting tension of the strips with rubbed endothelium was not altered by the addition of hemoglobin. That of the strips with intact endothelium, however, was enhanced and EDR to ACh was completely blocked From these results, we suggest that extracellular $Ca^{2+}$ is necessary for ACh-induced slow relaxation while $Ca^{2+}$ antagonists have not any effect on EDR.

• Journal of Chest Surgery
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• v.31 no.2
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• pp.102-107
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• 1998

It has not been clear whether L-arginine plays solely a role contributing to vascular nitric oxide (NO) synthesis. To investigate the mechanisms by which L-arginine induces vasorelaxation, effects of L-arginine on the isometric tension, and tissue NOx and cyclic guanosine monophosphate(cGMP) contents were examined in the isolated rat thoracic aorta. L-Arginine induced a dose-dependent relaxation of aortic rings only with intact endothelium only. The vasorelaxation response to low concentrations of L-arginine was abolished by the pretreatment with NG-nitro-L-arginine methyl ester(L-NAME, 10-4 mol/L), whereas the relaxation caused by higher concentrations L-arginine(10-5-10-3 mol/L) was maintained and even more pronounced in the presence of L-NAME. L-Arginine did not affect the vascular tension precontracted with KCl. The vascular tissue contents of NOx/cGMP were not significantly affected by L-arginine, while they were decreased by L-NAME. L-Arginine could not completely recover the NOx/cGMP decreased by L-NAME. Methylene blue only partially antagonized the relaxation response to L-arginine. Indomethacin did not affect the L-arginine-induced vasorelaxation, whereas ouabain markedly attenuated the relaxation. It is suggested that L-arginine induces vasorelaxation not only through its contribution to NO synthesis, but also through enhancing another endothelium-dependent mechanism which is NO/cGMP-independent and cyclooxygenase- independent.

• Journal of Haehwa Medicine
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• v.21 no.2
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• pp.85-94
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• 2013

단삼(丹蔘) (Salvia miltiorrhiza)은 꿀풀과(일과(―科) Lamiaceae)에 속하는 다년생 초본으로, 중국이 원산지이며 약용하기 위해 우리나라에서도 널리 재배하고 있다. 신농본초경(神農本草經) 상품(上品)에 수재(收載)되어 있으며, 거어지통(祛瘀止痛), 양혈소종(凉血消腫), 청심제번(淸心除煩), 활혈조혈(活血調血) 등의 효능이 있어 부인과 질환에 많이 사용되고 있는 약재에 속한다. 본 연구에서는 단삼(丹蔘) 추출물이 흰쥐의 흉부 대동맥 절편에 어떠한 양상으로 작용하는지 확인하고자 하였으며, 그 결과 단삼 추출물 특히 헥산 분획에서 강력한 혈관 이완 작용이 나타났으며, 혈관 내피 세포의 존재 유무에 상관없이 농도 의존적으로 혈관을 이완시켰으나 혈관 내피 세포가 존재하는 상황에서 더욱 강력한 혈관 이완 작용을 보였다. 이러한 과정에 NO에 의한 cGMP 증가가 주요하게 작용하는 것으로 추정되었으며, 칼슘 통로 차단 효과에 의한 세포 내 $Ca^{2+}$의 감소도 관여하는 것으로 생각된다.

• Journal of Ginseng Research
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• v.26 no.1
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• pp.1-5
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• 2002

It has been well known that Korea red ginseng has an antihypertensive effect. The antihypertensive effect may be due to its ability to change the peripheral resistance. Change of vascular tone in the resistance-sized artery contribute to the peripheral resistance, thereby regulate the blood pressure. Therefore, we investigated to clarify the vasorelaxing mechanism induced by crude saponin of Korea red ginseng in the resistance-sized mesenteric artery of rats. The resistance-sized mesenteric artery was isolated and cut into a ring. The ring segment was immersed in HEPES-buffered solution and its isometric tension was measured using myograph force-displacement transducer. Crude saponin of ginseng relaxed the mesenmetric arterial rings precontracted with norepinephrine (3$\mu$M) in dose-dependent manner (0.01 mg/㎖ -1 mg/㎖. The relaxation by crude saponin was smaller in endothelium-intact preparation than that in endothelium-denuded preparation. The contraction induced by A23187 or phorbol 12,13-dibutyrate was not affected by crude saponin of ginseng. The vasorelaxing effect of crude saponin of ginseng was significantly attenuated by the increase of the extracellular K$\^$+/ concentration. Crude saponin-induced vasorelaxation was not affected by tetraethylammonium (1 mM), glybenclamide (10$\mu$M), and 4-aminopyridine (0.1 mM) in these preparations. Ba$\^$2+/(10$\mu$M ∼100$\mu$M) markedly reduced the crude saponin-induced vasorelakation dose-dependently. From the above results, we suggest that crude saponin of ginseng may stimulate K$\^$+/ efflux and hyperpolarize the membrane, thereby cause the vasorelaxation in the resistance-sized mesenteric artery of rats.

• Journal of Chest Surgery
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• v.37 no.3
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• pp.210-219
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• 2004

Extracellular $K^{+}$ concentration ([ $K^{+}$]$_{0}$ ) can be increased within several mM by the efflux of intracellular $K^{+}$. To investigate the effect of an increase in [ $K^{+}$]$_{0}$ on vascular contractility, we attempted to examine whether extracellular $K^{+}$ might modulate vascular contractility, endothelium-dependent relaxation (EDR) and intracellular $Ca^2$$^{+}$ concentration ([C $a^2$$^{+}$]$_{i}$ ) in endothelial cells (EC). We observed isometric contractions in rabbit carotid, superior mesenteric, basilar arteries and movse aorta. [C $a^2$$^{+}$]$_{i}$ was recorded by microfluorimeter using Fura-2/AM in EC. No change in contractility was recorded by the increase in [ $K^{+}$]$_{0}$ from 6 to 12 mM in conduit artery such as rabbit carotid artery. whereas resistant vessels, such as basilar and branches of superior mesenteric arteries (SMA), were relaxed by the increase. In basilar artery, the relaxation by the increase in [ $K^{+}$]$_{0}$ to from 1 to 3 mM was bigger than that by the increase from 6 to 12 mM. In contrast, in branches of SMA, the relaxation by the increase in [ $K^{+}$]$_{0}$ to from 6 to 12 mM is bigger than that by the increase from 1 to 3 mM. $Ba^2$$^{+}$ (30 $\mu$M) did not inhibit the relaxation by the increase in [ $K^{+}$]$_{0}$ from 1 to 3 mM but did inhibit the relaxation by the increase from 6 to 12 mM. In the mouse aorta without the endothelium or treated with $N^{G}$_nitro-L-arginine (30 $\mu$M), nitric oxide synthesis blocker, the increase in [ $K^{+}$]$_{0}$ from 6 to 12 mM did not change the magnitude of contraction induced either norepinephrine or prostaglandin $F_2$$_{\alpha}$. The increase in [ $K^{+}$]$_{0}$ up to 12 mM did not induce contraction of mouse aorta but the increase more than 12 mM induced contraction. In the mouse aorta, EDR was completely inhibited on increasing [ $K^{+}$]$_{0}$ from 6 to 12 mM. In cultured mouse aorta EC, [C $a^2$$^{+}$]$_{i}$ , was increased by acetylcholine or ATP application and the increased [C $a^2$$^{+}$]$_{i}$ , was reduced by the increase in [ $K^{+}$]$_{0}$ reversibly and concentration-dependently. In human umbilical vein EC, similar effect of extracellular $K^{+}$ was observed. Ouabain, a N $a^{+}$ - $K^{+}$ pump blocker, and N $i^2$$^{+}$, a N $a^{+}$ - $Ca^2$$^{+}$ exchanger blocker, reversed the inhibitory effect of extracellular $K^{+}$. In resistant arteries, the increase in [ $K^{+}$]$_{0}$ relaxes vascular smooth muscle and the underlying mechanisms differ according to the kinds of the arteries; $Ba^2$$^{+}$-insensitive mechanism in basilar artery and $Ba^2$$^{+}$ -sensitive one in branches of SMA. It also inhibits [C $a^2$$^{+}$]$_{i}$ , increase in EC and thereby EDR. The initial mechanism of the inhibition may be due to the activation of N $a^{+}$ - $K^{+}$pump. activation of N $a^{+}$ - $K^{+}$pump.p.p.p.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.231-238
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• 1994

Backgroud: Since the demonstration of the fact that vascular relaxation by acetylcholine(Ach) results from the release of relaxing factor from the endothelium, the identity and physiology of this endothelium-derived relaxing factor(EDRF) has been the target for many researches. EDRF has been identified as nitric oxide(NO). With the recent evidences that EDRF is an important mediator of vascular tone, there have been increasing interests in defining the role of the EDRF as a potential mediator of hypoxic pulmonary vasoconstriction. But the role of EDRF in modulating the pulmonary circulation is not compeletely clarified. To investigate the endothelium-dependent pulmonary vasodilation and the role of EDRF during hypoxic pulmonary vasoconstriction, we studied the effects of $N^G$-monomethyl-L-arginine(L-NMMA) and L-arginine on the precontracted pulmonary arterial rings of the rat in normoxia and hypoxia. Mothods: The pulmonary arteries of male Sprague Dawley(300~350g) were dissected free of surrounding tissue, and cut into rings. Rings were mounted over fine rigid wires, in organ chambers filled with 20ml of Krebs solution bubbled with 95 percent oxygen and 5 percent carbon dioxide and maintained at $37^{\circ}C$. Changes in isometric tension were recorded with a force transducer(FT.03 Grass, Quincy, USA) Results: 1) Precontraction of rat pulmonry artery with intact endothelium by phenylephrine(PE, $10^{-6}M$) was relaxed completely by acetylcholine(Ach, $10^{-9}-10^{-5}M$) and sodium nitroprusside(SN, $10^{-9}-10^{-5}M$), but relaxing response by Ach in rat pulmonary artery with denuded endothelium was significantly decreased. 2) L-NMMA($10^{-4}M$) pretreatment inhibited Ach($10^{-9}-10^{-5}M$)-induced relaxation, but L-NMMA ($10^{-4}M$) had no effect on relaxation induced by SN($10^{-9}-10^{-5}M$). 3) Pretreatment of the L-arginine($10^{-4}M$) significantly reversed the inhibition of the Ach ($10^{-9}-10^{-5}M$)-induced relaxation caused by L-NMMA($10^{-4}M$) 4) Pulmonary arterial contraction by PE($10^{-6}M$) was stronger in hypoxia than normoxia but relaxing response by Ach($10^{-9}-10^{-5}M$) was decreased, 5) With pretreatment of L-arginine($10^{-4}M$), pulmonary arterial relaxation by Ach($10^{-9}-10^{-5}M$) in hypoxia was reversed to the level of relaxation in normoxia. Conclusion: It is concluded that rat pulmonary arterial relaxation by Ach is dependent on the intact endothelium and is largely mediated by NO. Acute hypoxic pulmonary vasoconstriction is related to the suppression on NO formation in the vascular endothelium.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.85-85
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• 1993

뇌동맥계는 일과성 저혈압에 반응하여 혈관확장이 야기되고, 혈압 상승시에는 혈관수축이 일어남으로서 뇌혈류가 일정하게 조절된다. 이러한 자가조절은 뇌손상 등의 병적 상태에서 야기된다. 연구의 목적은 \circled1 Cromakalim, CGRP(calcitonin-gene related peptide), 및 substance P에 의하여 뇌연막동맥의 직경이 어떻게 변동하는가를 관찰하고 \circled2 이들 신경성 peptide의 작용에 대하여 $K^{＋}$ 통로 개방 봉쇄제인 glibenclamide의 전처치 효과를 검색하고 \circled3 Capsaicin 전처치가 뇌혈류 자가조절에 어떻게 영향을 미치는가를 검색하였다. 그 결과는 다음과 같다. 1. 뇌혈류 자가조절은 대퇴동맥을 통한 사혈에 의하여 혈압하강을 일으킬 때 뇌연막 동맥은 이완하였고, reservoir내의 혈액을 체내로 주입함로서 혈압반전을 일으켰을 때는 혈관 수축이 일어났다. 2. 연막동맥은 glibenclamide (1~3$\mu$M)의 관류에 의하여는 영향을 받아니하였다. 3. 혈압변동에 따른 혈관직경의 변화를 회기직선으로 분석하였다. Glibenclamide 1과 3$\mu$M의 전처치 관류에 의하여 혈압하강에 따른 혈관 이완경사도와 혈압반전에 따른 혈관수축 경사도가 대조군에 비하여 현저히 약화되었다. 4. Cromakalim (0.1-30$\mu$M)의 각 농도를 대뇌표면에 관류시 연막동맥의 기초직경은 약물농도에 의존하여 증가되었고, 이는 glibenclamide (1$\mu$M) 전처치 관류에 의하여 억제되었다. 5. CGRP (0.1~100 nM)와 substance P (0.1~10nM)도 용량에 의존하여 혈관이완을 일으켰다. 전자는 glibenclamide (1$\mu$M) 전처치 관류에 의하여 억제되었으나 후자는 영향을 받지 아니하였다. 6. Capsaicin(50 nmol: intracisternally) 주사에 의하여 뇌혈류자가조절의 변동이 초래되었다. 이상의 결과들을 종합하면 CGRP가 혈압변동에 의하여 반사적으로 유리되고, 이는 glibenclamide-sensitive $K^{＋}$ 통로에 작용하는 것으로 시사된다.

• Journal of the Korea Convergence Society
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• v.8 no.2
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• pp.291-297
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• 2017

This study was aimed to secure the basis for developing the hangbang-tea may help promote healthy blood vessels by natural herbal ingredients formulated in accordance with the basic principles of oriental medicinal theory. We investigated the vessels contracted by concentrations and safety assessment carried out by the cell viability of Taraxaci Herba, Gardeniae Fructus, Chrysanthemum indicum and Lonicerae Flos composition and concentration. We found cell survival were higher than the control group show a beneficial trend in the growth of normal liver and kidney cells. As a results of this study will be the basis to develop the hangbang-tea differentiated in the future oriental medicine resources. Medicinal resources will be hangbang-tea based on clinical trials utilizing herbal western and oriental medicine convergence principle and vascular relaxation mechanism.

• Korean Journal of Ichthyology
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• v.12 no.1
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• pp.38-45
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• 2000

Depending on the fish species the vascular tone is distinctively regulated by numerous vasoactive substances. In most fish species the regulatory role of autonomic neurotransmitters and other vasoactive substances are not well defined. This research was designed to delineate the regulatory role of various endogenous autonomic neurotransmitters known to be important in mammalian vascular systems on isolated Israeli carp ventral aorta. Acetylcholine(ACh) contracted the aorta regardless of the pre-existing level of vascular tone, and the contraction was almost completely abolished by a cholinergic-muscarinic antagonist atropine. Endogenous, multiple receptor ($\alpha$ and $\beta$)-acting adrenergic agonist epinephrine (Epi) relaxed the vessel in the presence and absence of the pre-existing tones. Another endogenous multiple receptoracting agonist norepinephrine (NE) weakly contracted the aorta in non-preconstrcted state, but the response was reversed to relaxation when preconstricted. Isoproterenol, ${\alpha}\;{\beta}$ adrenergic receptor agonist, was a potent vasodilator whereas an ${\alpha}_1$ agonist phenyephrine was a contractor. The ${\alpha}_2$ adrenergic receptor agonist clonidine has not any significant effect in altering the vascular tone. The vasorelaxing action of Epi, NE and isoproterenol was significantly attenuated by $\beta$ receptor antagonist propranolol. These results imply that ACh may primarily play a contractor role via muscarinic receptor activation while adrenergic agonists, Epi and NE, are relaxants through activation of $\beta$ adrenergic receptors in vivo.