• Journal of Chest Surgery
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• 제29권12호
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• pp.1299-1305
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• 1996

고칼륨과 저온이 혈관내피세포의 acetylcholine(Ach)에 의한 혈관이완에 미치는 영향을 알아보기 위하여 흰쥐의 흉부 대동맥을 이용하여 Ach과 sodium nitroprusside(SNP)에 대한 이완 반응을 측정하였다. 실험은 다섯 군으로 나누어서 실시하였으며 각 군을 10례로 하였다. 1군은 대조군으로 어떤 조작도 가하지 않고 organ bath에서 등랑성 긴장도를 측정하였고, 2군(내피세포 제거군)은 내피세포를 물리적으로 제거후 1군과 같은 방법으로 긴장도를 측정하였고, 37$^{\circ}C$ 57에 45분간 처리후 혈관의 등장성 긴장도를 측정하였다. 대조군, 457,4mST및 3757군에서의 Ach에 대한 혈관의 이완은 유의한 차이가 없었으며,내피세포 제거군에서는 Ach에 대한 혈관의 이완이 대조군에 비해 현저하게 감소되었으며, SUP에 대한 혈관의 이완은 모든 군에서 유의한 차이가 없었다. 이에 저자들은 다음과 같은 결론을 내릴 수 있었다. 고농도의 칼륨과 저온자체는 흰쥐의 흉부대동맥 내피세포의 Ach에 대한 이완능을 저해하지 않는다.

• 동의생리병리학회지
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• 제33권4호
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• pp.198-206
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• 2019

This study was conducted to evaluate the vasorelaxant effect of DangGuiSu-San and SamHwangSaSim-Tang extract on contracted rabbit carotid artery. To study the effect of DangGuiSu-San and SamHwangSaSim-Tang extract on contracted rabbit carotid arterial strips, arterial strips with intact or damaged endothelium were used for experiment using organ bath. The pre-contracted arterial strips with Phenylephrine(PE) was treated with various concentrations of DangGuiSu-San and SamHwangSaSim-Tang extract(0.01, 0.03, 0.1, 0.3 and $1.0mg/m{\ell}$). To determine the mechanisms of DangGuiSu-San and SamHwangSaSim-Tang-induced vasorelaxant, DangGuiSu-San and SamHwangSaSim-Tang extract were infused into contracted arterial rings which had been pretreated by indomethacin(IM), tetraethylammonium chloride(TEA), $N{\omega}$-nitro-L-arginine ($_L-NNA$), methylene blue(MB). And calcium chloride(Ca) 1 mM was infused into precontracted arterial ring induced by PE after treatment of DangGuiSu-San and SamHwangSaSim-Tang extract in $Ca^{2+}$-free krebs solution. DangGuiSu-San and SamHwangSaSim-Tang extract revealed significant relaxation on PE-induced arterial contraction. DangGuiSu-San and SamHwangSaSim-Tang extract also had an effective relaxation to the intact endothelium arterial ring. SamHwangSaSim-Tang extract on contracted rabbit carotid artery is related with NO-cGMP pathway. Pretreatment of DangGuiSu-San and SamHwangSaSim-Tang extract inhibited the contraction by influx of extracellular $Ca^{2+}$ in contracted arterial ring induced by NE. This study indicated that the relaxation effect of SamHwangSaSim-Tang extract on contracted rabbit carotid artery is related with NO-cGMP pathway. Pretreatment of DangGuiSu-San and SamHwangSaSim-Tang extract inhibited the contraction by influx of extracellular $Ca^{2+}$ in contracted arterial ring induced by NE.

• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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• pp.375-382
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• 1999

Growing evidence indicates that enhanced generation or actions of nitric oxide (NO) are implicated in the pathogenesis of hypertension in spontaneously hypertensive rats and diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. We investigated whether inducible nitric oxide synthase (iNOS) expression in STZ-induced diabetic rats is responsible for the alterations of vascular reactivity. Diabetic state was confirmed 28 days after injection of STZ (i.p) in rats by measuring blood glucose. In order to evaluate whether short term (4 weeks) diabetic state is related with altered vascular reactivity caused by iNOS expression, isometric tension experiments were performed. In addition, plasma nitrite/nitrate (NOx) levels and expression of iNOS in the lung and aorta of control and STZ-treated rats were compared by using Griess reagent and Western analysis, respectively. Results indicated that STZ-treated rats increased the maximal contractile response of the aorta to phenylephrine (PE), and high $K^+,$ while the sensitivity remained unaltered. Endothelium-dependent relaxation, but not SNP-mediated relaxation, was reduced in STZ-treated rats. Plasma nitrite/nitrates are significantly increased in STZ-treated rats compared to controls. The malondialdehyde (MDA) contents of liver, serum, and aorta of diabetic rats were also significantly increased. Furthermore, nitrotyrosine, a specific foot print of peroxynitrite, was significantly increased in endothelial cells and smooth muscle layers in STZ-induced diabetic aorta. Taken together, the present findings indicate that enhanced release of NO by iNOS along with increased lipid peroxidation in diabetic conditions may be responsible, at least in part, for the augmented contractility, possibly through the modification of endothelial integrity or ecNOS activity of endothelium in STZ-diabetic rat aorta.

• The Korean Journal of Physiology
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• 제29권1호
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• pp.61-67
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• 1995

The extract of Ginkgo bibloba (EGb) is a complex mixture of natural products from the Ginkgo leaves and clinically used for the treatment of cerebral and peripheral circulatory disturbances due to its combined activity of several vasoactive principles. In this study we investigated the action of EGb and its mechanism in isolated rabbit corporal smooth muscle to evaluate the possibility of using this material as a pharmacoerecting agent. Strips of rabbit corpus cavernosum were mounted in organ chambers to measure isometric tension. EGb began to exert an relaxing effect at 1 mg/ml in the submaximally precontracted muscle strips with phenylephrine $(PHE,\;5{\times}10^{-6}\;M)$; causing concentration-dependent relaxation with maximal effect at $3{\sim}5\;mg/ml$. That relaxation was partially inhibited by removal of the smooth muscle endothelium or by pretreatment with a NO scavenger, pyrogallol $(10^{-4}\;M)$ or the guanylate cyclase inhibitor, methylene blue $(10^{-4}\;M)$. Pretreatment with EGb (3 mg/ml) inhibited PHE- $(5{\times}10^{-6}\;M)$ or KCI- (20 and 40 mM) induced contraction of muscle strip. In calcium-free high potassium solution EGb depressed the basal tone of the depolarized muscle strip and inhibited calcium-induced contraction when $CaCl_2$ $(10^{-4}\;M)$ was added. These results suggest that EGb relaxes rabbit corpus cavernosal smooth muscle through multiple action mechanisms that include increasing the release of nitric oxide from the corporal sinusoidal endothelium, sequestration of intracytosolic calcium, and maybe a hyperpolarizing action.

• Journal of Chest Surgery
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• 제37권3호
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• pp.210-219
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• 2004

외부 자극에 의하여 세포 내 $Ca^2$$^{+}$이 증가하면 세포 내 $K^{+}$이 유출되어 세포 외 $K^{+}$ 농도는 수 mM 범위에서 증가할 수 있다. 이러한 세포 외 $K^{+}$의 증가가 혈관 수축성에 미치는 영향을 규명하고자, 세포 외 $K^{+}$가 혈관평활근 수축성, 내피세포 의존성 이완과 혈관내피세포 $Ca^2$$^{+}$ 농도에 미치는 영향을 알아보고자 하였다. 토끼에서 분리한 경동맥, 상장간막동맥 분지, 기저동맥과 쥐의 대동맥에서 등장성 수축을 기록하였으며 배양한 쥐의 대동맥 혈관내피세포와 인간 제대정맥 내피세포에서 세포 내 $Ca^2$$^{+}$ 변화를 측정하였다. 세포 외 $K^{+}$ 농도를 6에서 12 mM로 증가하는 경우 도관동맥인 토끼 경동맥은 수축성에 변화가 없는 반면 저항혈관인 기저동맥과 상장간막동맥분지는 이완하였다. 이러한 $K^{+}$ 유발 이완은 혈관 종류에 따라 차이가 있었는데 기저동맥에서는 세포 외 $K^{+}$ 농도를 6에서 12 mM로 증가하였을 때보다 세포 외 $K^{+}$ 농도를 1에서 3 mM로 증가하였을 때 더 크게 이완하였으며 상장간막동맥의 분지에서는 반대로 세포 외 $K^{+}$ 농도를 6에서 12 mM로 증가하였을 때 더 크게 이완하였다. 그리고 세포 외 $K^{+}$ 농도를 6에서 12 mM로 증가하였을 때의 이완은 $Ba^2$$^{+}$에 의하여 억제되는 반면 1에서 3 mM로 증가에 의한 이완은 억제되지 않았다. 쥐 대동맥에서도 토끼 경동맥과 동일한 효과가 관찰되었는데 세포 외 $K^{+}$ 농도를 6 mM에서 12 mM로 변화시켜도 norepinephrine혹은 prostaglandin $F_2$$_{\alpha}$에 의한 수축력은 유의한 변화가 없었다. 또한 세포 외 $K^{+}$ 농도를 점차 증가시키는 경우 12 mM 이상 증가가 되면 혈관평활근이 수축하기 시작하였지만 12 mM 이하의 증가에 의해서는 혈관평활근의 수축력은 증가하지 않았다. 한편 쥐 대동맥에서 acetylcholine에 의하여 유발된 내피세포 의존성 이완은 세포 외 $K^{+}$ 농도를 정상 6 mM에서 12 mM로 증가시키면 억제되었다. 한편 배양한 쥐 대동맥 내피세포에서는 acetylcholine 혹은 ATP에 의하여 세포 내 $Ca^2$$^{+}$이 증가하였다. 증가한 세포 내 $Ca^2$$^{+}$은 세포 외 $K^{+}$농도를 6 mM에서 12 mM로 증가시키면 가역적 및 농도 의존적으로 감소하였다. 세포 외 $K^{+}$ 증가에 의한 세포 내 $Ca^2$$^{+}$ 억제 효과는 인간 제대정맥 내피세포에서도 관찰되었다. 그리고 세포 외 $K^{+}$ 증가에 의한 내피세포 의존성 이완의 억제효과는 $Na^{+}$- $K^{+}$ pump 억제제인 ouabain과 $Na^{+}$-C $a^2$$^{+}$exchanger 억제제인 N $i^2$$^{+}$에 의하여 억제되었다. 이러한 실험 결과로 미루어 세포 외 $K^+$의 증가는 저항혈관 평활근을 이완시키는데 그 기전은 혈관 종류에 따라 차이가 있었다. 그리고 세포 외 $K^{+}$의 증가는 혈관내피세포 $Ca^2$$^{+}$을 감소시켜 내피세포 의존성 이완을 억제하는데 이는 $Na^2$$^{+}$- $K^2$$^{+}$pump를 활성화시켜 일어나는 것으로 생각된다.

• 동의생리병리학회지
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• 제27권6호
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• pp.730-737
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• 2013

The purpose of this study is to investigate vasorelaxant effect of Epimedium koreanum(EK) extract on rabbit carotid artery. In this study, to determine vasorelaxant effect of EK extract on rabbit carotid artery, arterial rings with intact or damaged endothelium were used for experiment using organ bath, and were contracted by norepinephrine(NE). After being contracted, arterial rings were treated with EK extract in a dose-dependent manner To study its mechanism, the contracted arterial rings induced by NE were pretreated with indomethacin(IM), $N_{\omega}$-nitro-L-arginine(L-NNA), methylene blue(MB) or tetraethylammonium chloride(TEA) and 0.1 $mg/m{\ell}$ EK extract was added. To analyze the effect of the EK extract on influx of extracellular calcium chloride($Ca^{2+}$) in rabbit carotid artery, in $Ca^{2+}$-free krebs solution, krebs solution containing 1 mM $Ca^{2+}$ was infused into the contracted arterial ring by NE after pretreatment of EK extract. To measure the cytotoxicity of the EK extract, cell viability of human umbilical vein endothelial cell(HUVEC) was measured by MTT assay, and nitric oxide(NO) was measured by Griess reagent. The EK extract significantly was relaxed the arterial ring with intact endothelium contracted by NE, but the vasorelaxant effect of the EK extract was inhibited in the arterial rings with damaged endothelium. The vasorelaxant effect of the EK extract was not different between the IM-pretreatedand and non-treated arterial rings. The vasorelaxant effect of EK extract were significantly inhibited, when arterial rings were pretreated with L-NNA, TEA, MB. And in $Ca^{2+}$-free krebs solution, increasing of arterial contraction by $Ca^{2+}$ addition were also inhibited by the treatment of EK, but not significant. The treatment of EK extract was increased NO concentration in HUVEC. This study suggested that the vasorelaxant effect of EK extract would be related with EDHF and NO production and increasing of cyclic GMP.

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

• 동의생리병리학회지
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• 제16권5호
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• pp.938-942
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• 2002

We have examined the relaxational response to the water extract of Rheum palmatum L.(ERP) and water extrc alcohol processed Rheum palmatum L.(ARP) in isolated thoracic aorta from sprague dawley (SD) rat. Rat thoracic aort investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to ERP and ARP investigated in vessels precontracted with 5-hydroxytryptamine(5-HT). We found that the thoracic aorta segments respo to ERP and ARP with a dose-dependent vasorelaxation. We found that ; The thoracic aorta segments responded to I and ARP with a dose-dependent vasodilation. The 5-HT induced contraction at 10/sup -4/M were inhibited by 71.7% and a: after addition of the 0.01 g/mL water extract of ERP and ARP. The 5-HT induced contraction at 10/sup -4/M were inhibite 100% after 10/sup -3/M emodin. The concentration of emodin was 0.027% and 0.098% in ERP and ARP. In condusion, ERP ARP induced relaxation in the isolated rat thoracic aorta were composed of dose-dependent relaxation. and it has pi vasodilation.

• 대한약리학회지
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• 제25권1호
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• pp.43-51
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• 1989

내피세포가 잘 보존된 개 신동맥에서 Phenylephrine으로 전 수축시킨 후 Actylcholine을 투여하면 혈관 이완을 관찰할 수 있었지만 내피세포를 파괴시킨 개 신동맥에서는 혈관 이완을 관찰할 수 없었으므로 내피세포가 혈관 이완에 관여함을 알 수 있었다. 그래서 내피세포에서 분비되어 혈관 이완을 촉진하는 물질을 Endothelium Dependent Relaxation Factor (EDRF)라고 한다. Acetylcholine에 의한 혈관 이완은 Atropine에 의해 경쟁적으로 억제되었으므로 Muscarinc 수용체의 자극을 받아 EDRF가 분비되고 이것이 평활근에 작용하여 이완을 일으킬 것으로 생각되었다. EDRF의 작용기전을 알아보기 위해 용해성 Guanylate cyclase 억제제인 Methylene blue를 전처치 했을 때는 Acetylcholine 뿐 만 아니라 Sodium nitroprusside에 의한 이완도 억제되었다. 그러나 Prostacyclin에 의한 이완은 억제되지 않았다. 이 결과로 판단 해 보면 EDRF에 의한 이완효과가 Cyclic GMP와 관련이 있을 것으로 생각되었다. 한편 Thromboxane $A_2$ 유사체인 U-46619로 전수축 시킨 후 Alpha-2 아드레날린성 항진제인 Clondine을 투여했을 때 혈관 이완은 일어나지 않았다. 수축의 억제 양상에 있어서 Alpha-1 아드레날린성 항진제인 Phenylephrine보다 Clonidine이 더 효과적 이었다. 이상의 결과를 기초로 하여 다음과 같은 결론을 얻을 수 있었다. 1) Muscarinic 수용체의 자극을 받아 EDRF의 분비가 촉진된다. 2) Alpha-1 아드레날린성 수용체와 Alpha-2 아드레날린성 수용체가 개 신동맥에 존재한다. 3) EDRF에 의한 이완이 Methylene blue에 의해서 억제되므로 cGMP를 이용한 기전 임을 알 수 있었다.단요수근신건과 외상과의 변화를 알 수 있으며 진단에 있어서 보조적인 역할을 할 수 있다. 하지만, 치료 후 증상 호전 도달기간의 예후 판정에는 크게 도움이 되지 않는다. 시술과정에서 코일의 이탈이 2예에서 발생하였으나, 모두 snare기법으로 제거되었고, 그 밖의 다른 합병증은 없었다. 결론: 만성골반통을 일으키는 골반울혈증후군의 치료에 있어서 코일을 이용한 난소정맥색전술은 단기추적검사상 다수에서 증상의 소실 및 완화를 보여 비교적 효과적이고 안전한 방법으로생각되며, 다른 병인이 공존하지 않는다면 기존의 수술적 치료를 대치할 수 있는 훌륭한 중재적 치료법으로써 이용될 수 있을 것으로 사료된다. 있게 큰 수치를 보였다. 결론: 정상 두개내혈관 직경은, 성별 차이가 40대에서 분명하였고 남자가 여자에 비하여 크거나 큰 경향을 보였으며, 중뇌동맥 직경은 성별에 상관없이 고령층이 저령층에 비하여 의미있게 크거나 큰 경향을 나타내었다. 고령층의 중뇌동맥 근위부 직경은 남자가 2.59$\pm$0.35 mm, 여자가 2.38$\pm$0.37 mm이었고, 원위부 직경은 남자가 2.63$\pm$0.43 mm, 여자가 2.39$\pm$0.35 mm 이었다.고 Monaliza Finely Soft는 23% 더 높은 분리율을 나타냈으므로 선충분리용(線蟲分離用)으로는 향수처리(香水處理)되지 않은 것이 더 좋은 것으로 사료(思料)된다. 4. 온도별(溫度別) 선충분리율(線蟲分離率)을 $15^{\circ},\;25^{\circ}\;and\;35^{\circ}C$에서 조사(調査)한 결과(結果) 전체적(全體的)으로 $35^{\circ}C$에서 분리율(分離率)이 가장 높게 나타났다. 5. 시간경과(時間經過)에 따른 선충분리율(線蟲分離率)은 12시간(時間) 후(後)가 35.3 %이고 24시간(時間) 후(後)가 40.

• 대한본초학회지
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• 제25권4호
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• pp.17-21
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• 2010

Objectives : The aim of this study was to evaluate the differential mechnism of vasodilation of alcohol steamed Rhei Tangutici Radix et Rhizoma. (ART) and Rhei Tangutici Radix et Rhizoma. (RT) in rat thoracic aorta. Methods : Rat aortic ring preparations were mounted in organ baths with oxygenated (95% $O_2$-5% $CO_2$) Krebs-Ringer bicarbonate solutions at $37{\pm}0.5^{\circ}C$ and subjected to contractions or relaxations. Results : ART exerted vasorelaxation on phenylephrine(PE)-induced contraction in a dose dependent manner. Vasorelaxation effects of ART and RT were endothelium-independent. In the $Ca^{2+}$-free high KCl (60 mM) baths, the contraction of aortic rings induced by accumulative addition of $Ca^{2+}$ (0.3-10.0 mM) was significantly reduced by pre-treatment with both ART and RT for 10 min. The magnitude of vasodilatation was biggerin ART. Moreover, verapamil ($0.001{\mu}M$) and diltiazem ($10{\mu}M$), voltage operative $Ca^{2+}$channel blockers, attenuated the relaxation effect of ART but not that of RT. In the absence of extracellular $Ca^{2+}$, pre-incubation of the aortic rings with RT ($1.0mg/m{\ell}$) significantly reduced the contraction caused by PE but not that of ART. $K^+$ channel inhibitors such as glibenclamide (Gli, $10^{-5}M$), tetraethylammonium (TEA, 1 mM) and 4-aminopyridine (4-AP, 0.2 mM) significantly reduced the ART's vasorelaxation efficacy, but not that of RT. However, the relaxation effects of ART and RT were not inhibited by pre-treatment with indomethacin ($10^{-5}M$), and atropine ($10^{-6}M$). Conclusions : These results suggest that the endothelium-independent relaxation is due to inhibition of $Ca^{2+}$ influx via the suppression of $Ca^{2+}$ release from intracelluar store in RT but via both voltage operative $Ca^{2+}$channel blockage and $K^+$ channel activation in ART.