• Herbal Formula Science
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• v.7 no.1
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• pp.167-181
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• 1999

Rhizoma Arisaematis, Lignum Akebiae, Rhizoma Zedoariae, Cortex Eucommiae, Folium Perillae, Radix Sophorae Subprostratae, Radixi, Radix Ledeboutriellae, Rhizoma Atractylodis, Herba Ephedrae, Radix Puerariae and Radi Aconitx Bupleuri have been used in Korea for many centuries as a treatment for various disease. The purpose of the present study is to determine the effect of several herbs on norepinephrine(NE) induced blood vessel contraction in rabbits and pigs. Rabbit(2 kg, male) were killed by $CO_2$ exposure and a segment (8-10mm) of each rabbit was cut into equal segments and mounted in a tissue bath. Contractile force was measured with force displacement transducers under 2-3 g loading tension. The dose of norepinephrine(NE) which evoked 50% of maximal response $(ED_{50})$ was obtained from cumulative dose response curves for NE $(10^{-6}{\sim}10^{-3}M)$. Contractions evoked by NE $(ED_{50})$ were inhibited significantly by Rhizoma Arisaematis, Lignum Akebiae, Rhizoma Zedoariae, Cortex Eucommiae, Folium Perillae, Radix Sophorae Subprostratae and Herba Ephedrae in abdominal aorta. Contractions evoked by NE $(ED_{50})$ were inhibited significantly be Lignum Akebiae, Rhizoma Zedoariae, Cortex Eucommiae, Herba Ephedrae, Radix Puerariae and Radix Bupleuri in femoral artery. Contractions evoked by NE $(ED_{50})$ were inhibited significantly by Radix Sophorae Subprostratae, Radix Aconiti and Herba Ephedrae in renal artery. These results indicate that each herb can relax NE induced contraction of rabbit and pig blood vessel selectively, and that this relaxation relates to Gui-Gyung(歸經).

• Journal of Environmental Science International
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• v.12 no.10
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• pp.1131-1136
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• 2003

To examine whether salt stress would alter or not contractility of isolated rat aorta, under anesthesia with sodium pentobarbital(50 mg kg-1 i.p.), male Sprague Dawley rats(300-330 g) were subjected to 0, 50, and 150 mM of sodium chloride at 37$^{\circ}C$ for 60 min. where as the sham group was left at modified Krebs-bicarbonate solution. To measure contractile response of vascular ring preparation isolated from rat was determined in organ bath and was recorded on physiograph connected to isometric transducer. And the strip was checked for expression of heat shock protein(Hsp) by Western blotting. One, three and eight hours later, we measured vascular contractility of isolated rat aorta treated with KCI, phenylephrine from organ bath study. The dose-vascular responses of potassium chloride and phenylephrine showed a little augmentation by NaCl concentration in the strips exposed to NaCl for 8 hours. And the response of relaxation induced by nitroprusside and acetylcholine was not influenced by NaCl stress in isolated aorta ring for 8 hours, respectively. Expression pattern of Hsp 70 of vascular muscle in isolated rat aorta showed a little increase in 150 mM NaCl group at 8 hours after NaCl treatment but not at 3 hours, and Hsp 60 expression of rat aorta was markedly increased in 50 mM NaCl group at 8 hours after NaCl treatment. Taken together, NaCl induced dose-and time dependent accumulation of the Hsp but not affected contraction of rat aorta. These data suggest that short term high salt stress was not sufficient to induce hypertension of rat aorta.

• Korean Journal of Acupuncture
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• v.17 no.1
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• pp.67-73
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• 2000

The purpose of the present study is to determine the effect of Radix Stemonae on histamine induced tracheal smooth muscle contraction in guinea pigs. Guinea pig(500g, male) were killed by $CO_2$ exposure and a segment (8-10mm) of the thoracic trachea from guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine (His) which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for histamine ($10^{-7}∼10^{-4}M$). Contractions evoked by His ($ED_{50}$) were inhibited significantly by Radix Stemonae. In guinea pig tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was 87.4% (p<0.01) after $100{\mu}l/ml$ Radix Stemonae. Following treatment with propranolol, the mean percent inhibition caused by $100{\mu}l/ml$ Radix Stemonae fell to 16.2% in guinea pig induced by histamine contraction. Indomethacin and methylene blue($10^{-7}M$) did not significantly alter the inhibitory effect of Radix Stemonae. These results indicate that Radix Stemonae can relax histamine induced contraction of guinea pig tracheal smooth muscle, and that this inhibition involves sympathetic effects.

• The Korean Journal of Physiology
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• v.20 no.1
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• pp.125-133
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• 1986

The effect of ethanol on the contraction of intestinal smooth muscle in Na-free solution was studied using cat ileal longitudinal muscle strips. Ethanol $(0.5{\pm}4%)$ inhibited both the spontaneous mechanical activity and base-line tension in normal physiological salt solution. However, in Na-free solution it induced a reversible contraction. The excitatory effect by ethanol in Na-free solution was increased with increasing the concentrations of ethanol and the time incubated in Na-free solution. The excitatory response by ethanol was reduced by increasing the concentrations of Na in incubated medium . Ethanol-induced contractile response was not affected by $Ca^{2+}$ removal in bathing medium. In Na-free solution, the contraction by ethanol was inhibited by Las. but was not affected by verapamil. The contraction induced by Na removal in solution was inhibited by the pretreatment of ethanol. These results suggest that ethanol may induce the contraction by increasing the release of superficially membrane-bound $Ca^{2+}$ and/or intracellular $Ca^{2+}$ in Na-free physiological salt solution.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.629-638
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• 2006

This study was carried out to examine the relaxational response to the water extract of Sobokchuko-tang (SCT) in rat thoracic aorta. Segments of thoracic aorta obtained from rats immediately after delivery were mounted in organ baths superfused on a polygraph. It was found that the thoracic aorta segments responded to the SCT with dose-dependent vasorelaxation. At $10^{-7}M$ phenylephrine-induced contraction, the contractile response of thoracic aortic rings were inhibited by 99.2%. 75.3%. 42.4% and 35.8% after addition of the respective concentration (1O. 30. 100. $300{\mu}g$/ml) of SCT. This vasorelaxation of rat thoracic aorta was endothelium-dependent. The action mechanisms of vasorelaxation are thought to be concerned with the role of NO. cAMP and cyclooxygenase. but not with cGMP.

• Biomolecules & Therapeutics
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• v.20 no.4
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• pp.386-392
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• 2012

The endothelin (ET) signaling pathway controls many physiological processes in myocardium and often becomes upregulated in heart diseases. The aim of the present study was to investigate the effects of ET receptor upregulation on the contractile function of adult ventricular myocytes. Primary cultured adult rat ventricular myocytes were used as a model system of ET receptor overexpression in the heart. Endothelin receptor type A ($ET_A$) or type B ($ET_B$) was overexpressed by Adenoviral infection, and the twitch responses of infected ventricular myocytes were measured after ET-1 stimulation. Overexpression of $ET_A$ exaggerated positive inotropic effect (PIE) and diastolic shortening of ET-1, and induced a new twitch response including twitch broadening. On the contrary, overexpression of $ET_B$ increased PIE of ET-1, but did not affect other two twitch responses. Control myocytes expressing endogenous receptors showed a parallel increase in twitch amplitude and systolic $Ca^{2+}$ in response to ET-1. However, intracellular $Ca^{2+}$ did not change in proportion to the changes in contractility in myocytes overexpressing $ET_A$. Overexpression of $ET_A$ enhanced both systolic and diastolic contractility without parallel changes in $Ca^{2+}$. Differential regulation of this nature indicates that upregulation of $ET_A$ may contribute to diastolic myocardial dysfunction by selectively targeting myofilament proteins that regulate resting cell length, twitch duration and responsiveness to prevailing $Ca^{2+}$.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.37-42
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• 2012

The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibitory responses to melatonin, melatonin-pretreated muscle strips were exposed to a calcium channel antagonist (verapamil), three potassium channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644), and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93). Melatonin pretreatment ($10^{-8}{\sim}10^{-6}M$) decreased the contractile responses induced by PE ($10^{-9}{\sim}10^{-4}M$) and Ach ($10^{-9}{\sim}10^{-4}M$) in a dose-dependent manner. Melatonin ($10^{-7}M$) also blocked contraction induced by high KCl ($[KCl]_{ECF}$; 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin ($10^{-7}M$) potentiated the relaxation response of the strips by verapamil, but other potassium channel blockers did not change melatonin activity. Melatonin pretreatment significantly decreased contractile responses induced by Bay K 8644 ($10^{-11}{\sim}10^{-7}M$). KN-93 enhanced melatonin-induced relaxation. The present results suggest that melatonin can inhibit bladder smooth muscle contraction through a voltage-dependent, calcium-antagonistic mechanism and through the inhibition of the calmodulin/CaMKII system.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.37-44
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• 2017

Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that $kr{\ddot{u}}ppel$-like factor 8 (KLF8) is essential for tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with $TNF{\alpha}$ significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by $TNF{\alpha}$ stimulation in an ERK-dependent manner. The promoter region of KLF8 contained putative Sp1, KLF4, and $NF{\kappa}B$ binding sites. Myocardin significantly enhanced the promoter activity of KLF4 and KLF8. The ectopic expression of KLF4 strongly enhanced the promoter activity of KLF8. Moreover, silencing of Akt1 significantly attenuated the promoter activity of KLF8; conversely, the overexpression of Akt1 significantly enhanced the promoter activity of KLF8. The promoter activity of SMA, $SM22{\alpha}$, and KLF8 was significantly elevated in the contractile phenotype of VSMCs. The ectopic expression of KLF8 markedly enhanced the expression of SMA and $SM22{\alpha}$ concomitant with morphological changes. The overexpression of KLF8 stimulated the promoter activity of SMA. Stimulation of VSMCs with $TNF{\alpha}$ enhanced the expression of KLF5, and the promoter activity of KLF5 was markedly suppressed by KLF8 ectopic expression. Finally, the overexpression of KLF5 suppressed the promoter activity of SMA and $SM22{\alpha}$, thereby reduced the contractility in response to the stimulation of angiotensin II. These results suggest that cross-regulation of KLF family of transcription factors plays an essential role in the VSMC phenotype.

• Journal of Life Science
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• v.20 no.6
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• pp.831-837
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• 2010

KR-31125 (2-butyl-5-dimethoxymethyl-6-phenyl-7-methyl-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine) is a potent inhibitor of angiotensin II type 1 ($AT_1$) receptors in human recombinant $AT_1$ receptors and rabbit aorta. These in vitro studies revealed that KR-31125 inhibited specific [$^{125}I$] [$Sar^1$, $Ile^8$]-angiotensin II binding to human recombinant $AT_1$ receptors in a concentration dependent manner with an $IC_{50}$ value of $19.72{\pm}2.65$ nM. However, no interaction with $AT_2$ receptors was detected as displayed by the competition binding of [$^{125}I$] CGP 42112A to human recombinant $AT_2$ receptor. The binding action was also confirmed as a competitive mode that was identical to the previously studied compound, losartan. In addition, KR-31125 caused a nonparallel shift to the right in the concentration response curves to angiotensin II with a 30-80% decrease in the maximum contractile responses ($pK_B$: 7.63). Compared to the previous studies with losartan that showed a parallel right shift in the maximum contractile responses to AII ($pA_2$: 7.59), KR-31125 presented a different mode of action with a similar potency to losartan. These results demonstrate that KR-31125 is a highly potent and $AT_1$ selective angiotensin II receptor antagonist that can be applied to the fields of new diagnostic and research tools with upcoming in vivo study results.

• YAKHAK HOEJI
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• v.41 no.6
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• pp.802-816
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• 1997

In order to investigate the pharmacological properties of New Woohwangehungsimwon Pill (NWCH). Effects of Woohwangehungsimwon Pill (WCH) and NWCH were compared using various experimental models. In isolated rat aorta, NWCH and WCH showed the relaxation of blood vessels in maximum contractile response to phenylephrine ($10^{-6}$M) without regard 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 relaxative effects of NWCH and WCH. NWCH and WCH inhibited the vascular contractions induced by acethylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats(SHRs), NWCH and WCH decreased significantly heart rate. These, at high doses, had a negative inotropic effect that was a decrease of LVDP 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, these had no effects on parameters of action potential at low doses, whereas inhibited the cardiac, contractility at high doses. Furthermore, these had a significant inhibitory effects on heart acceleration in normotensive rats and SHRs. These results suggested that NWCH and WCH have weak cardiovascular effects, and that there is no significant differences between two preparations.