• 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.

• The Korean Journal of Physiology
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• 제24권1호
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• pp.77-90
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• 1990

There have been conflicting reports concerning the effect of Panax ginseng on the contractility of vascular smooth muscle, i.e., Panax ginseng extract has been reported to cause relaxation, contraction or to have no effect on the tension of vascular smooth muscle. A further investigation of $Ca^{++}$ stores which supply $Ca^{++}$ for contraction of vascular smooth muscle is needed to understand the underlying mechanisms of this conflicting effect of ginseng alcohol extract (GAE). The present study was intended to examine the sources of calcium mobilized for contraction of vascular smooth muscle by GAE. Aortic ring preparations were made from the rabbit thoracic aorta and endothelial cells were removed from the ring. The contractility of the aortic ring was measured under various experimental conditions and $Ca^{++}$ flux across the membrane of aortic ring and the sarcoplasmic reticulum and mitochondria were measured with a calcium selective electrode. The result were summarized as follows; 1) At low concentration of extracellular $Ca^{++}$, GAE increased the contractility of vascular smooth muscle in dose-dependent fashion except high concentration $Ca^{++}$ (1 mM). 2) In the presence of ryanodine, GAE still increased contractility of vascular smooth muscle as much as control group, but in the presence of caffeine, GAE increased it significantly. i.e. Their effects seemed to be additive. 3) In the presence of verapamil+lanthanum, and verapamil+lanthanum+ryanodine, the contractility of the vascular smooth muscle was decreased, but a dose dependent increase in vascular tension was still demonstrated by GAE although total tension was low. 4) GAE increased $Ca^{++}$ efflux from vascular smooth muscle cells, but have no effect on $Ca^{++}$ influx. 5) GAE increased $Ca^{++}$ efflux from sarcoplasmic reticulum and mitochondria vesicles. From the above results, it may be concluded that GAE increased the release of $Ca^{++}$ from sarcoplasmic reticulum, mitochondria or other intracellular $Ca^{++}$ stores of vascular smooth muscle, but it does not increase $Ca^{++}$ influx across the plasma membrane.

• 대한약리학회지
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• 제29권1호
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• pp.65-72
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• 1993

자외선조사는 흰쥐흉부대동맥의 휴지기장력에 거의 영향을 미치지 못했으나, phenylephrine으로 수축된 표본에서는 자외선조사로 내피세포가 존재하면 수축반응을, 내피세포가 제거되면 이완반응이 나타났다. 이 수축반응은 조사시간의 길이($10{\sim}320$초)에 비례하여 증가하였으나 이완반응은 그렇지 못하였다. 내피세포 존재표본에서 자외선의 수축반응은 phenylephrine농도의 증가($10^{-7}{\sim}10^{-5}M$) 그리고 $acetylcholine(10^{-6}M)$, $isoproterenol(10^{-7}M)$ 및 $nitroglycerin(3.5{\times}10^{-8} M)$의 추가투여시 크게 강화되었다. 그러나 $phentolamine(10^{-6}M)$ 또는 $LY83583(10^{-7},10^{-6}M)$의 추가투여시에는 자외선 수축반응이 억제 또는 이완반응으로 역전되었다. 내피세포 제거표본에서의 자외선 이완반응은 phenylephrine농도의 증가 그리고 isoproterenol, nitroglycerine, phentolamine 및 LY83583의 추가투여시 유의하게 감약되었다. 이상의 성적은 흰쥐 적출 흥부대동맥에서 자외선조사는 내피세포 존재유무에 따라 수축과 이완반응이 각각 나타나며, 수축반응은 자외선에 의한 EDRF 유리억제 또는 부분적으로 어떤 EDCF와도 관련이 있음을 시사하고 있다.

• 대한수의학회지
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• 제43권3호
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• pp.361-371
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• 2003

The vasorelaxant actions and blood pressure lowering of the ${\alpha}_2$-adrenoceptor agonists (${\alpha}_2$-AAs) clonidine and xylazine were investigated in rat isolated aortic rings and anesthesized rats. Both clonidine and xylazine produced a concentration-dependent inhibition of the sustained contraction induced by norepinephrine (NE), but not by KCl. NE-induced contractions were attenuated partly by nifedipine or verapamil, voltage dependent $Ca^{2+}$ channel blockers. These $Ca^{2+}$ channel blockers-resistant contractions were abolished by clonidine or xylazine. Inhibitory effects of a ${\alpha}_2$-AAs on contractions could be reversed by ryanodine, an intracellular $Ca^{2+}$, transport blocker, and tetrabutylammonium (TBA), a $Ca^{2+}$ activated $K^+$ channel blocker, but not by nifedipine, glibenclamide or removal of extracellular $Ca^{2+}$ and endothelium. Moreover, ${\alpha}_2$-AAs produced relaxation in NE-precontracted isolated intact aortic rings in a concentration-dependent manner, but not in KCl-precontracted rings. The relaxant effects of ${\alpha}_2$-AAs were inhibited by ryanodine and TBA, but not by nifedipine, glibenclamide, N (G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), 2-nitro-4-carboxyphenyl N,N-diphenylcarhurnte (NCDC), lithium sulfate, staurosporine or removal of extracellular $Ca^{2+}$ and endothelium. In vivo, infusion of xylazine elicited significant decrease in anerial blood pressure. This xylazinelowered blood pressure was completely inhibited by the intravenous injection of TBA, but not by the intravenous injection of glibenclamide, L-NNA, L-NAME, AG, nifedipine, lithium sulfate or saponin.. These findings showed that the receptor-mediated and ${\alpha}_2$-adrenoceptor A-stimulated endothelium-independent vasorelaxant effect may be explained by decreasing intracellular $Ca^{2+}$ release and activation of $Ca^{2+}$-activated $K^+$ channels, which may contribute to the hypotensive effects of ${\alpha}_2$-AAs in rats.

• The Korean Journal of Physiology
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• 제22권1호
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• pp.13-29
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• 1988

In order to elucidate the regulatory mechanism of intracellular calcium ion concentrations, contractions or contractures induced by $Na^{+}-removal$, calcium-application or ouabain-treatment as an index of $Na^+/Ca^{2+}$ exchange activity were studied in atrial muscle or vascular smooth muscle (aorta and renal artery) of the rabbit. The magnitude of low sodium contractures in atrial trabeculae increased with sigmoid shape when external sodium concentrations were reduced to sodium-free condition, whereas that of calcium contracture intensified in a parabolic pattern when external calcium concentrations were elevated to 8 mM. $Na^{+}-removal$ contractures were induced in a duration-dependent manner to $K^{+}-free$ exposure and same findings were observed with ouabain treatment. $Na^{+}-free$ contractures were not affected by verapamil treatment, but stimulated by $100{\mu}M\;Mn^{2+}$ and inhibited by high concentrations of $Mn^{2+}\;(2{\sim}8mM)$ in a dose-dependent manner. Ryanodine which is known to suppress the release of calcium from internal store abolished spontaneous twitch contractions induced by $K^{+}-free$ solution, but had no effect on the development $Na^{+}-free$ contractures. Na-free contractures were not always induced in vascular smooth muscle preparations. Contractures by $O\;mM\;Na^+$ were usually seen in aorta, but not often in renal artery.$50\;mM\;K^+$, noradrenaline (NA) and angiotensin II (AII) always evoked very large contraction in all preparations of vascular smooth muscle. Contractures developed by $O\;mM\;Na^+$ were not sensitive to verapamil treatment as in atrial trabeculae, but were abolished by $100{\mu}M\;Mn^{2+}$. In contrast to $Na^{+}-free$ contractures, $Mn^{2+}(100{\mu}M)$ had no effect on the contractures induced by NA or 50 mM$K^+$. Caffeine in the concentration of 10 mM evoked transient contracture in the distal renal artery. The rate of spontaneous relaxation in caffeine contracture was dependent upon the concentrations of external sodium, and had double component of relaxation when the rate of relaxation was plotted in the semilogarithmic scale of relative tension versus time. Especially late components of relaxation had more direct relation to $Na^+$ concentrations. It could be concluded that $Na^+/Ca^{2+}$ exchange mechanism in the heart has a large capacity, inhibited by $Mn^{2+}$ but not by verapamil and ryanodine, while $Na^+/Ca^{2+}$ exchange system in vascular smooth muscle has a very low capacity especially in small artery, inhibited by low concentration of $Mn^{2+}\;(100{\mu}M)$ but not affected by verapamil and ryanodine.

• 대한약리학회지
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• 제30권1호
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• pp.101-109
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• 1994

Tetrahydroisoquinoline유도체인 GS 283의 약리학적 특성을 흰쥐 흉부대동맥, 기니픽 결장띠 및 토끼 장간막 동맥 및 흰쥐 뇌를 사용하여 조사하였다. 혈관 평활근에서 GS283은 고 $K^+$에 의한 수축을 농도 의존적으로 억제하여 $Ca^{2+}$ 길항작용을 보였다. 또한 ${alpha}_1$- 수용체 자극에 의한 수축도 억제하였다. GS 283의 혈관이완 작용은 propranolol영향을 받지 않으므로 ${\beta}$-수용체 자극작용에 의한 것이 아니었다. 세포내 칼슘이온과 근장력 변화를 동시에 측정하였을 때 GS 283의 억제효과는 조직내 형광의 증가를 수반했다. 이 증가는 fura 2형광에 의한것이 아니라 내인성 pyridine nucleotide에 의한 것이며 이는 GS 283이 미토콘드리아 기능을 억제하는 효과가 있음을 시사했다. 흰쥐 뇌의 cAMP와 cGMP 의존성 phosphodiesterase에 대한 GS 283의 $K_i$,값은 2.5와 6.7mM이었다. 이상의 결과에서 GS 283의 약리 작용은 $Ca^{2+}$ 길항작용, ${\alpha}_1$- 수용체억제 작용 및 cyclic nucleotide 의존성 phosphodiesterase 억제 등 다양한 작용이 있으며 평활근 수축 억제에 대한 GS283 작용에는 $Ca^{2+}$ 길항이 가장 중요한 요인이 될 것으로 생각된다.

• 한국임상수의학회지
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• 제22권3호
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• pp.220-227
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• 2005

Although ketamine has been used in the field of anesthetic medicine for its safety and favourable respiratory effects, the cardiovascular effects of ketamine is still controversial. To clarify the action and mechanism of ketamine upon cardiovascular system, arterial blood pressure, tension of aortic ring, left ventricular developed pressure and heart rate were measured in rats, Ketamine produced two types of effects on arterial blood pressure in anesthetized rats; monophasic effect (blood pressure lowering) and biphasic effect (initial transient blood pressure increasing following sustained lowering), The ketamine-induced lowering of aterial blood pressure showed a concentration-dependent manner, inhibited by the pretreament of $MgCl_2$ and potentiated by the pretreatment of $CaCl_2$. The ketamine-induced lowering of aterial blood pressure was suppressed by the pretreatment of nifedipine, verapamil or lidocaine. In phenylephrine-precontracted endothelium intact (+E) aortic rings, ketamine sometimes caused a small enhancement of contraction ($112.5{\pm}3.6{\%}$). However, in many experiments, ketamine produced a concentration-dependent relaxation in +E aortic rings precontracted with either phenylephrine or KCl. Ketamine-induced relaxation was significantly greater in KCl-precontracted strips than phenylephrine-precontracted strips. In phenylephrine-precontracted +E aortic rings, the ketamine-induced vasorelaxation was not suppressed by endothelium removal or by the pretreatment of a nitric oxide synthase inhibitors, L-$N^G$-nitro-arginine and a guanylate cyclase inhibitors, methylene blue, suggesting that the ketamine-induced vasorelaxation is not dependent on the endothelial function. In addition, ketamine elicited an increase in left ventricular developed pressure in perfused hearts accompanied by decrease in heart rate. These results suggest that ketamine could evoke a hypotension due to vasorelaxation and decrease in heart rate in rats. The inhibitory effect of cardiovascular system might be associated with modulation of $Ca^{2+}$ homeostasis.

• Biomolecules & Therapeutics
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• 제5권3호
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• pp.239-245
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• 1997

Trimetoquinol (TMQ) and its analogs are known to have thromboxane $A_2$ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited $Ca^{2+}$ -induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to $\alpha$-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA$_2$ receptor but concerned with calcium antagonistic action and a-blocking action.n.

• 대한약리학회지
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• 제27권2호
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• pp.125-133
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• 1991

내피세포가 제거된 토끼의 적출 장간막 동맥에서 토끼의 대동맥 내피세포로 부터 A23187과 acetylcholine은 NO와 유사한 혈관 이완성 물질 (EDRF)을 유리한다. 이에 첨가하여 A23187은 acetylcholine과는 달리 superoxide anion에 의하여 파괴되지 않는 EDRF도 유리시킴을 확인하고 이의 특성에 대하여 연구하였다. 정상적인 생리영양액에서는 A23187과 acetylcholine의 용량-반응 곡선은 내피세포에 의존하지 않는 sodium nitroprusside의 곡선과 유사하였다. 이들은 methylene blue에 의하여 억제되었다. Hypoxanthine (HX)과 xanthine oxidase (XO)를 bath내로 투여시 phenylephrine에 의한 수축이 일과성으로 증가한 후 지속적으로 이완되었다. HX-XO 반응중에는 A23187은 장간막 동맥을 즉각적으로 이완시켰으나 acetylcholine의 이완작용은 소실되었다. A23187에 의하여 야기되는 장간막동맥의 이완은 50 mM $K^+-PSS$로 수축을 야기시켰을 때에는 나타나지 아니하였다. Superoxide dismutase를 전처치하였을 때는 HX-XO 반응중에도 acetylcholine 뿐만아니라 A23187에 의한 장간막 동맥의 수축은 이완되었다. 한편, acetylcholine에 의하여 야기되는 장간막 동맥의 이완은 A23187에 의하여 야기되는 이완에 비하여 phorbol 12-myristate 13-acetate (PMA)에 훨씬 더 민감하게 억제되었다. 내피세포의 기능과는 무관한 sodium nitroprusside에 의하여 야기되는 이완은 PMA에 의하여 영향을 받지 아니하였다. 이상의 결과로 미루어 볼때, A23187과 acetylcholine은 methylene blue에 의하여 억제되는 내피세포 의존성 이완을 야기시키고, 첨가하여 A23187은 어떤 병적 환경 아래서는 superoxide anion과 PMA에 저항성을 지닌 혈관이완성 물질을 유리하는 것으로 사료된다. 앞으로 A23187에 의하여 유리되는 혈관 이완성 물질이 superoxide anion에 의존하여 생성된 것인지에 대하여는 추후의 연구과제이다.

• Tuberculosis and Respiratory Diseases
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• 제38권3호
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• pp.270-279
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• 1991

It has been well known that the integrity of airway epithelium is important in developing of bronchial hyperreactivity or bronchial asthma. But the mechanisms underlying this nonspecific airway hyperresponsiveness are not yet determined. To evaluate the ability of guinea pig trachea to release an epithelium derived relaxing factor (EpDRF) which relax rat vascular smooth muscle, we performed the coaxial bioassay using guinea pig trachea and rat aorta. And to evaluate the nature of EpDRF we investigate the influence of methylene blue and indomethacin on the coaxial bioassay. Results were as follows. 1) Vascular smooth muscle mounted into the epithelium intact trachea which was precontracted with phenylephrine was relaxed by addition of histamine or acetylcholine. But vascular smooth muscle mounted into epithelium denuded trachea failed to be relaxed. 2) Epithelium dependent relaxation of vascular smooth muscle was not affected by pretreatment of methylene blue or indomethacin. These results strongly suggests that guinea pig tracheal epithelium releases EpDRF which is able to relax rat vascular smooth muscle. And EpDRF released by airway epithelium is not related to endothelium derived relaxing factor (EDRF) or cyclooxygenase products.