• The Korean Journal of Physiology
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• 제24권2호
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• pp.293-303
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• 1990

The contractile action of barium $(Ba^{2+})$ was investigated in the arterial strip of rabbit renal artery. The helical strip of isolated renal artery was immersed in the Tris-buffered Tyrode's solution equilibrated with 100% $O_2$ at $37^{\circ}C$ and its isometric tension was measured. $Ba^{2+}-induced$ contraction of arterial strip was dose-dependent and its maximal tension corresponded to $92.1{\pm}4.5%$ of tension by $K^+(100\;mM)$. $Ba^{2+}-induced$ contraction did not show the tachyphylactic phenomenon in the normal Tyrode's solution. $Ba^{2+}$ induced the tonic contraction in the $Ca^{2+}-free$ tyrode's solution and that was increased by the extracellula addition of $Ca^{2+}$. During the repeated exposure of the same dose of $Ba^{2+}\;(10\;mM)$ in the $Ca^{2+}-free$ Tyrode's solution, $Ba^{2+}-induced$ contraction was progressively decreased. Even though the intracellular NE-and caffeine-sensitive $Ca^{2+}$ was depleted, $Ba^{2+}$ induced the tonic contraction. After the pretreatment of lanthnum or verapamil, $Ba^{2+}$ did not induce contraction. $Ba^{2+}-induced$contraction was suppressed by extracellular $K^+$ in the normal Tyrode's solution and that was dependent on $K^+$ concentration. Suppressive effect of $K^+\;(14\;mM)$ on the $Ba^{2+}-induced$ contraction was also dependent on the intracellular $Ca^{2+}$ concentration. From the above resuts, it is suggested that $Ba^{2+}$ activate indirectly the contractile process by promoting the mobilization of intracellular $Ca^{2+}$ and the influx of extracellular $Ca^{2+}$. It is also suggested that action of $Ba^{2+}$ on the $Ca^{2+}-activated$ $K^+$ channel can result in the depolarization of cell membrane in the rabbit renal artery.

• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.36-44
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• 2006

진통과 해열작용을 가진 NSAIDs는 소화기계에 대한 부작용 때문에 COX-2 선택성 억제제로 대체되고 있다. 그러나 COX-2 선택적 억제제는 심혈관계에 대한 부작용이 보고되고 있어 혈관 평활근에 대한 직접적인 연구가 필요하다. 이에 본 연구에서는 혈관 반응성에 미치는 celecoxib와 aspirin, indomethacin의 영향을 비교 분석하였다. 또한 COX-1, COX-2 단백질 발현에 대한 indomethacin과 NO 공여제의 영향을 조사하였다. Phenylephrine 유발 수축반응에서 전처치 된celecoxib, indometacin, aspirin 순서로 혈관 반응성을 증가시켜, cyclooxygenase를 억제하면 혈관 수축성물질에 대한 반응성이 커질 수 있음을 나타낸다. 이중 cyclooxygenase에 대해 비가역적으로 강한 억제를 나타내는 aspirin이 제일 강한 효과를 나타내어 여기에 대한 연구는 더 필요할 것으로 생각된다. 혈관평활근 세포의 COX-2 단백질 발현은 indomethacin과 SNP, NOR-3 처치에 의해 증가되었으며, LPS를 이용하여 혈관염증을 유발 시키는 경우 혈관평활근 세포의 COX-2 단백질 발현이 증가되었고, 이 상태에서 SNP $100{\mu}M$ 전처치로 COX-2 단백질 발현을 감소되었으며, NOR-3 $100{\mu}M$은 COX-2 단백질 발현을 증가시켰다. LPS 유도 nitrite 생성에서 NOR-3는 SNP 보다 더 많은 nitrite를 생성시켰다. 이는 혈관의 수축반응에서 aspirin은 강한 상승작용을 유발하고, 혈관평활근 세포의 COX-2 발현은 NO 공여제, 혈관염증 유무에 따라 차이가 있는 것을 나타낸다.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.1-10
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• 1999

We sought to find out the mechanism of vascular relaxation by extracellular $K^+$ concentration $([K^+]_o)$ in the cerebral resistant arteriole from rabbit. Single cells were isolated from the cerebral resistant arteriole, and using voltage-clamp technique barium-sensitive $K^+$ currents were recorded, and their characteristics were observed. Afterwards, the changes in membrane potential and currents through the membrane caused by the change in $[K^+]_o$ was observed. In the smooth muscle cells of cerebral resistant arteriole, ion currents that are blocked by barium, 4-aminopyridine (4-AP), and tetraethylammonium (TEA) exist. Currents that were blocked by barium showed inward rectification. When the $[K^+]_o$ were 6, 20, 60, and 140 mM, the reversal potentials were $-82.7{\pm}1.0,\;-49.5{\pm}1.86,\;-26{\pm}1.14,\;-5.18{\pm}1.17$ mV, respectively, and these values were almost identical to the calculated $K^+$ equilibrium potential. The inhibition of barium-sensitive inward currents by barium depended on the membrane potential. At the membrane potentials of -140, -100, and -60 mV, $K_d$ values were 0.44, 1.19, and 4.82 ${\mu}M,$ respectively. When $[K^+]_o$ was elevatedfrom 6 mM to 15 mM, membrane potential hyperpolarized to -50 mV from -40 mV. Hyperpolarization by $K^+$ was inhibited by barium but not by ouabain. When the membrane potential was held at resting membrane potential and the $[K^+]_o$ was elevated from 6 mM to 15 mM, outward currents increased; when elevated to 25 mM, inward currents increased. Fixing the membrane potential at resting membrane potential and comparing the barium-sensitive outward currents at $[K^+]_o$ of 6 and 15 mM showed that the barium- sensitive outward current increased at 15 mM $K^+.$ From the above results the following were concluded. Barium-sensitive $K^+$?channel activity increased when $[K^+]_o$ is elevated and this leads to an increase in $K^+-outward$ current. Consequently, the membrane potential hyperpolarizes, leading to the relaxation of resistant arteries, and this is thought to contribute to an increase in the local blood flow of brain.

• 생명과학회지
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• 제28권12호
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• pp.1516-1522
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• 2018

죽상동맥경화는 대동맥의 만성염증에 의해 주로 발병되는 폐쇄동맥질환이다. 혈관평활근세포의 증식 및 이동은 죽상동맥경화 발병의 주된 병리적 반응이다. 본 연구에서는 죽상동맥경화 발병기전을 유도하는 표적 염증반응 물질의 탐색 및 이들에 의한 신호전달 기전을 연구하였다. 혈관평활근세포의 증식 및 이동은 prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$)에 의해 의미 있게 증가하였으나 tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$)에 의해서는 증가하지 않았다. Prostacyclin $I_2$ ($PGI_2$)는 혈관평활근세포의 증식은 촉진시켰으나 이동은 오히려 억제하였다. prostaglandin $D_2$ ($PGD_2$) 및 prostaglandin $E_2$ ($PGE_2$)는 혈관평활근세포의 증식을 촉진시켰으나 이동에는 영향을 미치지 않았다. $PGF_{2{\alpha}}$는 용량 의존적으로 혈관평활근세포의 증식 및 이동을 촉진시켰고 EC50는 약 $0.1{\mu}M$로 관찰되었다. 혈관평활근세포에서 phospholipase $C-{\beta}3$ ($PLC-{\beta}3$) 아형의 발현은 매우 높았으나 $PLC-{\beta}1$, $PLC-{\beta}2$, 및 $PLC-{\beta}4$의 발현은 관찰되지 않았다. U73122 처리를 통해 PLC의 활성을 억제하면 $PGF_{2{\alpha}}$에 의한 혈관평활근세포의 이동이 억제되었다. 또한 $PLC-{\beta}3$의 발현을 억제하면 $PGF_{2{\alpha}}$에 의한 혈관평활근세포의 증식 및 이동이 억제되었다. 이러한 결과들을 바탕으로 $PGF_{2{\alpha}}$ 는 혈관평활근세포의 증식 및 이동에 중요한 역할을 수행하고, 여기에는 $PLC-{\beta}3$가 필수적인 역할을 담당하고 있음을 제안한다.

• The Korean Journal of Physiology
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• 제15권1호
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• pp.61-66
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• 1981

In 1944 Cavallito and Bailey first extracted an essential oil, a powerful antibacterial principle, from the garlic and named it allicin. Later Stoll and Seeback elucidated that allicin was produced from alliin by the enzymatic action of arinase. Damaru observed the depressor responses following intraperitoneal administration of garlic juice in cats. And Thiersch presented evidence that garlic had a protective action against experimental arterosclerosis in cholesterol-fed animals. On the other hand it was also reported that anemias were caused by long-term ingestion of garlic as a result of reduction in hemoglobin and RBC. From the experiment in which the effect of garlic on the blood sugar level was studied, Lee insisted garlic elevated blood sugar level. However, August and Jain claimed that hypoglycemia was induced by garlic administration. Recently Bordia and Bansal suggested that essential oils extracted from onion and garlic have a strong preventive effect on hyperlipemia and prolonged coagulation time resulted from fat-feeding. Furthermore Bordia et al indicated that garlic exerted a strong fibrinolytic activity. In early 1920 s Sugihara reported that essential oil of garlic not only decreased arterial blood pressure but also had a paralytic effect on the isolated heart and intestinal strip of animals. The present study was proposed to investigate the effect of garlic juice and the mechanism of its action on the motility of the isolated rabbit duodenum. The motility of the isolated duodenum was recorded on polygraph by means of force transducer connected with Magnus apparatus. And the isolated duodenum was separtely pretreated with $acetylcholine(5{\times}10^{-7}\;gm/ml)$, $pilocarpine(2.5{\times}10^{-6}\;gm/ml)$, $histamine(5{\times}10^{-6}\;gm/ml)$ and barium $chloride(2.5{\times}10^{-5}\;gm/ml)$ in order to find out interations of these drugs with ASJ. The results obtained were as follows; At concentrations of 0.25%, 0.5% and 1.0% ASJ markedly inhibited contractions of isolated duodenum while tonus as well as contractility of the isolated intestine were decreased also with 0.5% and 1.0% ASJ. Since ASJ markedly abolished augmented motility of isolated intestine by histamine and partly reduced that by $BaCl_2$, it is strongly suggested that inhibitory action of ASJ on the intestinal motility is caused mainly by its antihistamine effect and partly by its direct action on the intestinal smooth muscle.

• Tuberculosis and Respiratory Diseases
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• 제62권5호
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• pp.421-426
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• 2007

진행성 간질환의 합병증으로 발생하는 문맥폐고혈압은, 이차성 폐동맥고혈압 중에서 진행성 간질환에 의한 문맥고혈압과 연관된 폐동맥고혈압으로 분류되며, 독특한 임상적, 병태생리학적 특징을 보인다. 임상양상은 점진적인 운동성 호흡곤란, 흉통 등을 호소하지만, 증상 없이 우연히 발견되는 경우도 있다. 심초음파 검사를 통해 예비적으로, 우심장 도관삽입으로 직접 우심실 및 평균 폐동맥압을 측정하여 진단할 수 있다. 치료는 칼슘통로차단제, 프로스타노이드 등을 사용하지만, 근본적인 치료를 위해서는 간 및 폐이식을 고려해야 한다. 저자들은 53세 여자로 20년 전에 간경변을 진단받은 후 호흡곤란으로 내원한 환자에게서, 간경변의 원인으로 원발성 담관성 간경변을 진단하고, 호흡곤란의 원인으로 문맥폐고혈압을 진단하여 치료하였기에 문헌고찰과 함께 보고한다.

• Journal of Pharmaceutical Investigation
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• 제33권4호
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• pp.311-317
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• 2003

Felodipine is a calcium antagonist that lowers blood pressure by reducing peripheral resistance by meas of a direct, selective action on smooth muscle in arterial resistance vessels. Futhermore, it have been approved for the effective in angina pectoris and cardiac failure. The purpose of the present study was to evaluate the bioequivalence of two felodipine extended release (ER) tablets, Splendil (YuHan Corporation) and Stapin (Hana Pharmaceutial Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The felodipine release from the two felodipine formulations in vitro was tested using KP VIII Apparatus II method at pH 6.5 buffer solution. Twenty six healthy male subjects, $22.73{\pm}1.78$ years in age and $66.66{\pm}7.28\;kg$ in body weight, were divided into two groups and a radomized $2{\times}2$ cross-over study was employed. After two tablets containing 5 mg as felodipine were orally administered, blood sample was taken at predetermined time intervals and the concentrations of felodipine in serum were determined using column-switching HPLC method with UV detector. The dissolution profiles of two formulations were similar at pH 6.5 buffer solution. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the Splendil were 2.53%, 1.32% and 18.32% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance rage of log(0.86) to log(1.25) $(e.g.,\;log(0.86){\sim}log(1.20)\;and\;log(0.89){\sim}log(1.23)\;for\;AUC_t,\;C_{max},\;respectively)$. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Stapin ER tablet and Splendil ER tablet are bioequivalent.

• Journal of Korean Neurosurgical Society
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• 제57권2호
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• pp.88-93
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• 2015

Objective : Elevated cellular retinoic acid binding protein-I (CRABP-I) is thought to be related to the abnormal proliferation and migration of smooth muscle cells (SMCs). Accordingly, a higher CRABP-I level could cause disorganized vessel walls by causing immature SMC phenotypes and altering extracellular matrix proteins which could result in vulnerable arterial walls with inadequate responses to hemodynamic stress. We hypothesized that elevated CRABP-I level in the cerebrospinal fluid (CSF) could be related to subarachnoid hemorrhage (SAH). Moreover, we also extended this hypothesis in patients with vascular malformation according to the presence of hemorrhage. Methods : We investigated the CSF of 26 patients : SAH, n=7; unruptured intracranial aneurysm (UIA), n=7; arteriovenous malformation (AVM), n=4; cavernous malformation (CM), n=3; control group, n=5. The optical density of CRABP-I was confirmed by Western blotting and presented as mean${\pm}$standard error of the measurement. Results : CRABP-I in SAH ($0.33{\pm}0.09$) was significantly higher than that in the UIA ($0.12{\pm}0.01$, p=0.033) or control group ($0.10{\pm}0.01$, p=0.012). Hemorrhage presenting AVM (mean 0.45, ranged 0.30-0.59) had a higher CRABP-I level than that in AVM without hemorrhage presentation (mean 0.16, ranged 0.14-0.17). The CRABP-I intensity in CM with hemorrhage was 0.21 and 0.31, and for CM without hemorrhage 0.14. Overall, the hemorrhage presenting group (n=11, $0.34{\pm}0.06$) showed a significantly higher CRABP-I intensity than that of the non-hemorrhage presenting group (n= 10, $0.13{\pm}0.01$, p=0.001). Conclusion : The results suggest that elevated CRABP-I in the CSF could be related with aneurysm rupture. Additionally, a higher CRABP-I level seems to be associated with hemorrhage development in vascular malformation.

• 대한본초학회지
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• 제30권6호
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• pp.69-75
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• 2015

Objectives : This study was designed to investigate effects of the combination with Korean Red Ginseng (Panax ginseng C.A. Meyer), Gastrodia Rhizoma (Gastrodia elata Blume) and Polygoni Multiflori Radix (Polygonum multiflorum Thunberg) on metabolic disorders including cholesterol and erectile dysfunction in hyperlipidemia rats.Methods : Animals were divided into six groups; Control with normal diet, high fat/cholesterol-diet (HFCD), fluvastatin, Korean Red Ginseng treated (KRG), and the combination treated (Korean Red Ginseng, Gastrodia Rhizoma and Polygoni Multiflori Radix; 1:1:1 for KGP1 and 2:1:1 for KGP2). The experimental groups initially received HFCD for 10 weeks and then treated orally with fluvastatin, KRG, KGP1 and KGP2 during the final 6 weeks. Erectile function was determined by the measurements of intracavernosal pressure (ICP) and maximal arterial pressure (MAP) after electrical stimulation of the cavernosal nerve.Results : KGP2 decreased the level of total cholesterol and LDL cholesterol in the sera of HFCD rats without no changes of body weights. KRG, KGP1 and KGP2 decreased the level of C-reactive protein (CRP) levels except of fluvastatin, synthetic HMG-CoA reductase inhibitor. KRG, KGP1 and KGP2 significantly increased the ICP, ICP/MAP ratio, area under the curve (AUC) compared with those of normal rat. Morphometric analyses showed that KRG, KGP1 and KGP2 increased the volume of smooth muscle and the regular arrangement of collagen fibers in corpus cavernosum of HFCD rats. The penile expression of eNOS was increased by KRG, KGP1 and KGP2.Conclusions : Based on these results, we suggest that the combination with Korean Red Ginseng, Gastrodia Rhizoma and Polygoni Multiflori may improve hyperlipidemia through regulating the lipid profiles and erectile dysfunction in rats.

• Tuberculosis and Respiratory Diseases
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• 제42권4호
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• pp.600-604
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• 1995

저지들은 캐나다 방문당시 복부 팽만감을 주소로 그곳 병원을 림프관평활근 종증을 진단받고 귀국 후 본 병원에서 매달 Depo provera를 근주하고 매달 폐기능 검사등을 실시하여 추적관찰하고 있는 폐와 후복강에 발생한 림프관평활근종증의 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다.