• YAKHAK HOEJI
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• v.41 no.6
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• pp.797-801
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• 1997

Recently we reported that water extracts of Coptidis Rhizomas showed calcium antagonistic action and alpha-adrenoceptor inhibitory action in the vascular smooth muscle. Since ca lcium antagonistic properties are important in the treatment of various diseases including asthma. In the present study, the bronchodilatory effects of crude extract of three kinds of Coptidis Rhizoma (Coptidis chinensis, Coptis japonica and root hair of Coptis japonica) was investigated using rat isolated trachea. The result showed that all extracts relaxed carbachol-contracted tracheal smooth muscle. Concentration-dependently, in which the root hair of Coptis japonica was the least potent. The inhibitory potency expressed in terms of $IC_{50}$ against carbachol contraction was 1.8${\mu}$g/ml and 2.7${\mu}$g/ml for Coptidis chinensis and Coptis japonica, respectively. These extracts also inhibited KCI-contracted tracheal smooth muscle. But the relative potency ($IC_{50}$) was 3.5 and 4.1 folds weaker than carbachol-induced contraction for Coptidics chinenesis and Coptis japonica, respectively. Pretreatment of crude extracts also inhibited carbachol- or KCI-induced contraction, non-competitively. These findings indicate that the extracts have muscarinic blocking as well as $Ca^{2+}$ channel blocking action. When provoked intracellular stored $Ca^{2+}$ release by carbachol in $Ca^{2+}$-free conditions, initial phasic contraction due to $Ca^{2+}$ release was significantly inhibited by the extracts. As taken together, we conclude that water extracts of Coptidis Rhizoma may be beneficial in bronchospasm or other broncheal tube narrowing conditions such as asthma.

• BMB Reports
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• v.47 no.6
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• pp.311-317
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• 2014

microRNAs (miRNAs) are a class of small, non-coding RNAs that play critical posttranscriptional regulatory roles typically through targeting of the 3'-untranslated region of messenger RNA (mRNA). Mature miRNAs are known to be involved in global cellular processes, such as differentiation, proliferation, apoptosis, and organogenesis, due to their capacity to target multiple mRNAs. Thus, imbalances in the expression and/or activity of miRNAs are involved in the pathogenesis of numerous diseases, including pulmonary arterial hypertension (PAH). PAH is a progressive disease characterized by vascular remodeling due to excessive proliferation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). Recently, studies have evaluated the roles of miRNAs involved in the pathogenesis of PAH in these pulmonary vascular cells. This review provides an overview of recent discoveries on the role of miRNAs in the pathogenesis of PAH and discusses the potential for miRNAs as therapeutic targets and biomarkers of PAH.

• The Korean Journal of Pharmacology
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• v.15 no.1_2 s.25
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• pp.29-37
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• 1979

The tension-length relationships and reactivity of vascular smooth muscle in longitudinal strips from portal vein ana in helical strips from thoracic aorta and pulmonary artery of normotensive control and cadmium-hypertensive rabbits were studied in vitro. 1. The mean arterial pressures of non-poisoned control rabbits was $87.0{\pm}4.7 mmHg$. However, Cd-poisoned group revealed the significant increase in pressure by $109.04{\pm}2.8 mmHg$ (p<0.005). 2. By tension-length studies, strips from portal vein of Cd-poisoned group stretched a greater percent increase in length in response to an applied resting force from 0.25 to 5 g than did those from non-poisoned group. On the contrary, strips from thoracic aorta of Cd-poisoned group showed less compliant than those from control, i.e. the former underwent a less percent increase in length than the latter. Passive tension-length relations of pulmonary artery was unaffected by Cd-hypertension. 3. The force of contraction(active tension) was significantly lowered in strips from aorta of Cd-hypertensive group throughout the range of $0.5{\sim}2g$ passive tension. However, there was no significant difference in the development of active tension of portal vein or pulmonary artery of both groups. 4. The $K^+$-contraction in the portal vein, aorta and pulmonary artery of Cd-poisoned group made no difference in the active force from those of control group. 5. The force of contraction in the strips from aorta of Cd-poisoned group was significanty decreased compared to that of control. The results suggested that the alterations in vascular reactivity to contracting substances and in distensibility to passive tension were induced in the Cd-hypertensive rabbits.

• Journal of Life Science
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• v.13 no.4
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• pp.441-447
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• 2003

To examine the role of protein kinase C (PKC) in regulation of interleukin-1 beta (IL-1$\beta$)-induced iNOS expression, IL-1$\beta$-induced nitrite production was observed in cultured vascular smooth muscle (VSM) cells pretreated with phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-butyrate (PDB) as PKC activator; 4$\alpha$-phorbol-didecanoate (PDD) as PKC non-activator. Nitrite production induced by IL-1$\beta$ was increased by the presence of increasing concentration of PMA ranging from 2 to 200 nM. However, in VSM cells pretreated with PMA and PDB, IL-1$\beta$-induced $NO_2$ production was decreased in proportion to the duration of pretreatment, and most significantly decreased in pretreatment time of 24 hours. Using RT-PCR method, the expression of iNOS mRNA induced by IL-1$\beta$ was decreased in VSM cells pretreated with PMA 200 nM for 24 hours. These results suggest that decrease in IL-I$\beta$-induced nitrite production by the pretreatment of PMA result from inhibition of iNOS expression and the inhibition related to PMA-induced PKC down-regulation.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.769-774
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• 1997

Non-neuronal high affinity binding sites for benzodiazepines have been found in many peripheral tissues including cardiac muscle and vascular smooth muscle, and have been designated as 'peripheral benzodiazepine receptor'. Benzodiazepines have been shown to induce relaxation of the ileal, vesical, and uterine smooth muscles. However, it is still unclear about possible involvement of peripheral benzodiazepine receptor on the contractility of trachealis muscle. This study was performed to investigate the role of the peripheral benzodiazepine receptor on the contractility of canine trachealis muscle. Canine trachealis muscle strips of 15 mm long were suspended in an isolated organ bath containing 1 ml of physiological salt solution maintained at $37^{\circ}C$, and aerated with $95%\;O_2/5%\;CO_2$. Isometric myography was performed, and the results of the experiments were as follows: Ro5-4684, FGIN-1-27 and clonazepam reduced a basal tone of isolated canine trachealis muscle strip concentration dependently, relaxant actions of RoS-4684 and FGIN-1-27 were antagonized by PK11195, a peripheral benzodiazepine receptor antagonist. Flumazenil, a central type antagonist, did not antagonize the relaxant action of Peripheral type agonists. Saturation binding assay of [3H]Ro5-4864 showed a high affinity$(Kd=5.33{\pm}1.27nM,\;Bmax=\;867.3{\pm}147.2\;fmol/mg\;protein)$ binding site on the canine trachealis muscle. Ro 5-4684 suppressed the bethanechol-, 5-hydroxyoyptamine- and histamine- induced contractions. Platelet activating factor (PAF) exerted strong and prolonged contraction in trachealis muscle strip. Strong tonic contraction by PAE was attenuated by Ro 5-4684, but not by WEB 2086, a PAF antagonist. Based on these results, it is concluded that the peripheral benzodiazepine receptor mediates the inhibitory regulation of contractilty of canine trachealis muscle.

• Journal of Life Science
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• v.18 no.6
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• pp.891-896
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• 2008

The function of mast cells as effector cells in allergy has been extensively studied. Mast cells activated through high affinity IgE-receptor ($Fc{\varepsilon}RI$) release diverse mediators, and lead to smooth muscle constriction, vasodilation, increase of vascular permeability, leukocyte recruitment and activation, mucus secretion, and tissue proliferation and remodeling. However, various other immunological and non-immunological signals can lead to the activation of mast cells. In resent years, mast cells have been identified to be involved in a complex range of immune functions. Mast cells can be important as key players in the regulation of innate as well as adapted immune responses, and may influence the development of allergy, autoimmune disorder and peripheral tolerance. This review summarizes the recent advances in the understanding of effector functions of mast cells in immune responses.

• Korean Journal of Veterinary Pathology
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• v.3 no.2
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• pp.73-76
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• 1999

The tissue distribution and cellular localization of viral antigen in the brain of aborted fetus with bovine viral diarrhea virus(BVDV) infection was studied; BVDV antigens was detected in spleen, kidney, lung, eyelid as well as brain. In the brain, the virus was recognized in neurons and non-neuronal cells in the cerebellum and cerebrum. Many cells in the superficial layer and occasional Purkinje cells had BVDV antigens. As well, BVDV was also found in the perivascular cells, vascular endothelial cells and smooth muscle cells in the vessels and neuroglial cells in the white matter. This finding suggests that BVD virus favors infect progenitor cells in the brain, notably in the superficial layer of cerebellum, and damage normal development of cerebellum, which leads to cerebellar hypoplasia.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.459-469
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• 1995

As S-nitrosothiols were proposed as nitrergic carriers in vascular and nonvascular smooth muscle, we have investigated the relaxant properties of several S-nitrosothiols in the porcine retractor penis(PRP) muscle and compared them with the effects of exogenously added NO, electrical field stimulation(EFS) of NANC nerves and sodium nitroprusside(SNP). Also the influences of oxyhemoglobin and hydroquinone on the relaxant responses were investigated. In addition, effects of NO on membrane potentials and its involvement in the generation of inhibitory junction potential(IJP) were investigated with conventional intracellular microelectrode technique. The results were summerized as follows. 1. Frequency-dependent relaxations of PRP muscle were induced by EFS to NANC nerve. Tetrodotoxin($1{\times}10^{-6}M$) abolished the relaxations of PRP muscle induced by EFS, and L-NAME(($2{\times}10^{-5}M$) and methylene blue($4{\times}10^{-5}M$) inhibited the relaxations. L-NAME-induced inhibition of the relaxations was reversed by L-arginine($1{\times}10^{-3}M$), but not by D-arginine. 2. Exogenous NO($1{\times}10^{-5}-1{\times}10^{-4}M$), sodium nitroprusside(($1{\times}10^{-7}-1{\times}10^{-4}M$) induced dose-dependent relaxations of PRP muscle. All S-nitrosothiols($1{\times}10^{-7}-1{\times}10^{-4}M$) tested relaxed the PRP muscle in dose-dependent manner and the potency order was SNAP>GSNO>CysNO>SNAC. 3. Oxyhemoglobin($5{\times}10^{-5}M$) blocked the relaxation induced by exogenous NO and inhibited EFS-, S-nitrosothiols-, and SNP-induced relaxation. 4. Hydroquinone($1{\times}10^{-4}M$) also abolished the relaxations induced by exogenous NO, and reduced the relaxations induced by S-nitrosothiols, but did not affect EFS- and SNP-induced relaxations. 5. SNP($2{\times}10^{-6}-5{\times}10^{-6}M$) relaxed muscle strips but the membrane potentials were not affected. 6. EFS with several pulses(1ms, 2Hz, 80V) produced an inhibitory junction potential(IJP) with muscle relaxation. They were abolished by TTX($2{\times}10^{-6}M$). $N^G$-nitro-$_{\small{L}}$-arginine(L-NNA, $2{\times}10^{-5}M$) abolished the muscle relaxation, but had no effect on IJP.

• Nutrition Research and Practice
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• v.13 no.4
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• pp.302-309
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• 2019

BACKGOURND/OBJECTIVES: Vascular inflammation is an important feature in the atherosclerotic process. Recent studies report that leaves and branches of Carpinus turczaninowii (C. turczaninowii) have antioxidant capacity and exert anti-inflammatory effects. However, no study has reported the regulatory effect of C. turczaninowii extract on the arterial inflammatory response. This study therefore investigated modulation of the arterial inflammatory response after exposure to C. turczaninowii extract, using human aortic vascular smooth muscle cells (HAoSMCs). MATERIALS/METHODS: Scavenging activity of free radicals, total phenolic content (TPC), cell viability, mRNA expressions, and secreted levels of cytokines were measured in LPS-stimulated (10 ng/mL) HAoSMCs treated with the C. turczaninowii extract. RESULTS: C. turczaninowii extract contains high amounts of TPC ($225.6{\pm}21.0mg$ of gallic acid equivalents/g of the extract), as well as exerts time-and dose-dependent increases in strongly scavenged free radicals (average $14.8{\pm}1.97{\mu}g/mL$ $IC_{50}$ at 40 min). Cell viabilities after exposure to the extracts (1 and $10{\mu}g/mL$) were similar to the viability of non-treated cells. Cytokine mRNA expressions were significantly suppressed by the extracts (1 and $10{\mu}g/mL$) at 6 hours (h) after exposure. Interleukin-6 secretion was dose-dependently suppressed 2 h after incubation with the extract, at $1-10{\mu}g/mL$ in non-stimulated cells, and at 5 and $10{\mu}g/mL$ in LPS-stimulated cells. Similar patterns were also observed at 24 h after incubation with the extract (at $1-10{\mu}g/mL$ in non-stimulated cells, and at $10{\mu}g/mL$ in the LPS-stimulated cells). Soluble intracellular vascular adhesion molecules (sICAM-1) secreted from non-stimulated cells and LPS-stimulated cells were similarly suppressed in a dose-dependent manner after 24 h exposure to the extracts, but not after 2 h. In addition, sICAM-1 concentration after 24 h treatment was positively related to IL-6 levels after 2 h and 24 h exposure (r = 0.418, P = 0.003, and r = 0.524, P < 0.001, respectively). CONCLUSIONS: This study demonstrates that C. turczaninowii modulates the arterial inflammatory response, and indicates the potential to be applied as a therapeutic use for atherosclerosis.

• Archives of Pharmacal Research
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• v.28 no.6
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• pp.709-715
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• 2005

The purpose of this study was to investigate the effect of atropine on peripheral vasodilation and the mechanisms involved. The isometric tension of rat mesenteric artery rings was recorded in vitro on a myograph. The results showed that atropine, at concentrations greater than 1$\mu$M, relaxed the noradrenalin (NA)-precontracted rat mesenteric artery in a concentration-dependent manner. Atropine-induced vasodilatation was mediated, in part, by an endothelium-dependent mechanism, to which endothelium-derived hyperpolarizing factor may contribute. Atropine was able to shift the NA-induced concentration-response curve to the right, in a non-parallel manner, suggesting the mechanism of atropine was not mediated via the ${\alpha}_1$-adrenoreceptor. The $\beta$-adrenoreceptor and ATP sensitive potassium channel, a voltage dependent calcium channel, were not involved in the vasodilatation. However, atropine inhibited the contraction derived from NA and $CaCl_2$ in $Ca^{2+}$-free medium, in a concentration dependent manner, indicating the vasodilatation was related to the inhibition of extracellular $Ca^{2+}$ influx through the receptor-operated calcium channels and intracellular $Ca^{2+}$ release from the $Ca^{2+}$ store. Atropine had no effect on the caffeine-induced contraction in the artery segments, indicating the inhibition of intracellular $Ca^{2+}$ release as a result of atropine most likely occurs via the IP3 pathway rather than the ryanodine receptors. Our results suggest that atropine-induced vasodilatation is mainly from artery smooth muscle cells due to inhibition of the receptor-mediated $Ca^{2+}$-influx and $Ca^{2+}$-release, and partly from the endothelium mediated by EDHF.