• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2001년도 학술 발표회 진행표 및 논문초록
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• pp.24-24
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• 2001

The present study was undertaken to determine whether p38 mitogen-activated protein kinase participates in the regulation of vascular smooth muscle contraction by endothelin-I (ET-1) in rat thoracic aorta. ET-1 induced a sustained contraction. In contrast, both the intracellular Ca$\^$2＋/ and myosin light chain (MLC) phosphorylations were not sustained.(omitted)

• IMMUNE NETWORK
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• 제9권3호
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• pp.106-113
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• 2009

Background: We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC. Methods: Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 ($AT_1$) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [$^3H$]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings. Results: Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the $AT_1$ receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an $AT_1$ receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor. Conclusion: These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.299-304
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• 2010

Losartan is a selective angiotensin II (Ang II) type 1 ($AT_1$) receptor antagonist which inhibits vascular smooth muscle cells (VSMCs) contraction and proliferation. We hypothesized that losartan may prevent cell proliferation by activating AMP-activated protein kinase (AMPK) in VSMCs. VSMCs were treated with various concentrations of losartan. AMPK activation was measured by Western blot analysis and cell proliferation was measured by MTT assay and flowcytometry. Losartan dose- and time-dependently increased the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in VSMCs. Losartan also significantly decreased the Ang II- or 15% FBS-induced VSMC proliferation by inhibiting the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. Compound C, a specific inhibitor of AMPK, or AMPK siRNA blocked the losartan-induced inhibition of cell proliferation and the $G_0/G_1$ cell cycle arrest. These data suggest that losartan-induced AMPK activation might attenuate Ang II-induced VSMC proliferation through the inhibition of cell cycle progression.

• 약학회지
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• 제53권3호
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• pp.156-160
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• 2009

The present study was undertaken to determine whether transgelin participates in the regulation of vascular smooth muscle contraction and, if so, to investigate the mechanism. By PCR homology cloning, the cDNA sequence of ferret transgelin was determined and phosphorothioate antisense and random oligonucleotides were synthesized and introduced into strips of ferret aorta by a chemical loading procedure. Treatment of ferret aorta with transgelin antisense oligonucleotides resulted in a significant decrease in protein levels of transgelin to sham- or random sequence-loaded muscles, but no change in the protein levels of actin. Contraction in response to a phorbol ester was significantly decreased in antisense-treated muscles compared to sham- or random sequence-loaded controls. Neither basal intrinsic tone nor the contraction in response to phenylephrine was significantly affected by the antisense treatment. The data indicate that transgelin plays a significant role in the regulation of contraction and suggest that in a tonically active smooth muscle transgelin may function as a signalling protein to facilitate PKC or ERK-dependent signalling rather than thick filament regulation including $Ca^{2+}$ or calmodulin dependent regulation of myosin light chain kinase.

• The Journal of Korean Physical Therapy
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• 제15권4호
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• pp.442-454
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• 2003

The aim of this study was to demonstrate the effects of silver spike point (SSP) low frequency electrical stimulation on plasma vasoactive intestinal polypeptide (VIP) activities measured by radioimmunoassay from volunteer and the effects of VIP on pain substance-induced contraction investigated by isometric tension methode in animal. The current of 3 Hz continue type, but not 100 Hz continue type, of SSP low frequency electrical stimulation significantly increased in plasma VIP from normal volunteer. The pain substance, such as norepinephrine, serotonin, and prostaglandin $F2{\alpha}$, increased vascular smooth muscle contraction, respectively. These responses were inhibited by VIP applied cumulatively (1 nM - $1\;{\mu}M$), but not serotonin-induced contraction. In addition, serotonin, and prostaglandin $F2{\alpha}$ induced uterine smooth muscle contraction from rat. However, these responses were inhibited by VIP ($1\;{\mu}M$), only serotonin-induced contraction. These results suggest that the VIP regulates pain substance in part and that the SSP low frequency electrical stimulation, specifically current of 3 Hz continue type, significantly increases plasma VIP from volunteer.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.69-74
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• 2016

The present study was undertaken to investigate the influence of cardamonin on vascular smooth muscle contractility and to determine the mechanism(s) involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Cardamonin significantly relaxed fluoride-, phenylephrine-, and phorbol ester-induced vascular contractions, suggesting that it has an anti-hypertensive effect on agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, cardamonin significantly inhibited the fluoride-induced increase in pMYPT1 level and phenylephrine-induced increase in pERK1/2 level, suggesting inhibition of Rho-kinase and MEK activity and subsequent phosphorylation of MYPT1 and ERK1/2. This study provides evidence that the relaxing effect of cardamonin on agonist-induced vascular contraction regardless of endothelial function involves inhibition of Rho-kinase and MEK activity.

• Journal of Korean Neurosurgical Society
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• 제38권5호
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• pp.375-379
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• 2005

Objective : Papaverine has been used in treating vasospasm following subarachnoid hemorrhage[SAH]. However, its action mechanism for cerebral vascular relaxation is not clear. Potassium channels are closely related to the contraction and relaxation of cerebral smooth muscle. Therefore, to identify the role of potassium and calcium channels in papaverine-induced vascular relaxation, we examine the effect of papaverine on potassium channels in freshly isolated smooth muscle cells from rat basilar artery. Methods : The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Papaverine was added to the bath solution. Results : Papaverine of $100{\mu}M$ into bath solution increased the amplitude of the outward $K^+$ current which was completely blocked by BKCa[large conductance calcium dependent potassium channels]blocker, IBX[iberiotoxin], and calcium chealator, BAPTA[l,2-bis[o-aminophenoxy]ethane-N,N,N',N'-tetraacetic acid], in whole cell mode. Conclusion : These results strongly suggest that potassium channels may play roles in papaverine-induced vascular relaxation in rat basilar artery.

• The Korean Journal of Physiology and Pharmacology
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• 제22권4호
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• pp.437-445
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• 2018

${\alpha}$-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in Schisandra chinensis (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms, but the mechanism responsible for this activity has not been determined. To determine the role played by ICB on the regulation of vascular tone, we investigated the inhibitory effects of ICB on vascular contractile responses by adrenergic ${\alpha}$-receptor agonists. In addition, we investigated the role on myosin light chain (MLC) phosphorylation and cytosolic calcium concentration in vascular smooth muscle cells (VSMC). In aortic rings isolated from C57BL/6J mice, ICB significantly attenuated the contraction induced by phenylephrine (PE) and norepinephrine (NE), whereas ICB had no effects on KCl (60 mM)-induced contraction. In vasculatures precontracted with PE, ICB caused marked relaxation of aortic rings with or without endothelium, suggesting a direct effect on VSMC. In cultured rat VSMC, PE or NE increased MLC phosphorylation and increased cytosolic calcium levels. Both of these effects were significantly suppressed by ICB. In conclusion, our results showed that ICB regulated vascular tone by inhibiting MLC phosphorylation and calcium flux into VSMC, and suggest that ICB has anti-hypertensive properties and therapeutic potential for cardiovascular disorders related to vascular hypertension.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.460-465
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• 2011

The present study was undertaken to investigate the influence of quercetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Quercetin at a low concentration (0.01-0.03 mM) directly and more significantly relaxed fluoride or thromboxane $A_2$-induced vascular contraction than phorbol ester-induced contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, quercetin more significantly inhibited thromboxane $A_2$-induced increases in pMYPT1 levels than phorbol ester-induced increases. It also more significantly inhibited thromboxane $A_2$-induced increases in pMYPT1 levels than pERK1/2 levels suggesting the mechanism involving the primarily inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1. This study provides evidence regarding the mechanism underlying the relaxation effect of quercetin on agonist-induced vascular contraction regardless of endothelial function.

• Journal of Chest Surgery
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• 제43권4호
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• pp.345-355
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• 2010

산성화를 초래하는 Hypoxia 등 여러 가지 조건에서 변화하는 세포외 pH 변화는 궁극적으로 세포내 pH 변화를 유발하며 세포 내외 pH 변화는 혈관평활근 수축성 변화를 유발한다. 이러한 세포 내외 pH 변화에 의한 혈관 수축성 변화 기전을 규명하고자, pH 변화가 혈관수축인자들에 의한 혈관평활근 수축, 혈관평활근세포내 $Ca^{2+}$ 농도, 그리고 혈관평활근의 $Ca^{2+}$에 대한 민감도에 미치는 영향을 알아보고자 하였다. 대상 및 방법: 쥐에서 분리한 상장간막동맥과 그 분지에서 등장성 수축을 기록하였으며 배양한 상장간막동맥 세포에서 세포내 $Ca^{2+}$ 변화를 측정하였다. 세포외 pH는 정상인 7.4에서 6.4, 6.9 혹은 7.8로 변화시켰으며, 세포내 pH 변화는 propionic acid나 $NH_4$를 투여하거나 ${\beta}$-escin으로 세포막의 투과성을 증가시켜 세포외 용액의 pH 변화로 유발시켰다. 결과: 세포외 pH를 7.4에서 6.9, 6.4로 감소시키면 노에피네프린과 세로토닌에 의한 용량-반응 곡선이 우측 이동하였으며 최대 수축력의 50% 수축력을 유발하는 농도(half maximal effective concentration)가 증가하였고, pH를 7.8로 증가시키면 그 반대 현상이 일어났다. 노에피네프린은 배양한 혈관평활근세포에서 세포내 $Ca^{2+}$ 농도를 증가시켰으며, 이 세포내 $Ca^{2+}$ 증가는 세포외 pH 감소에 의하여 억제되었으며 세포외 pH 증가에 의하여 증가하였다. 노에피네프린에 의한 수축은 세포내 pH를 감소시키는 $NH_4$에 의하여 억제된 반면, 안정 장력은 $NH_4$과 propionic acid에 의하여 증가하였다. ${\beta}$-escin으로 세포막의 투과도를 증가시킨 후 세포외 용액의 $Ca^{2+}$ 농도를 증가시켜 수축을 유발시킨 후 세포외 용액의 pH를 변화시키면 pH 감소에 의하여 수축력이 감소하였으며 증가에 의하여 수축력이 증가하였다. 결론: 세포외 pH의 감소는 혈관평활근의 수축성을 감소시키는데 이는 세포외 pH 감소에 의한 혈관평활근의 혈관수축물질에 대한 반응성 감소, 혈관평활근 세포내 $Ca^{2+}$ 유입 억제 그리고 $Ca^{2+}$에 대한 혈관평활근의 민감성 감소에 의하여 일어난 것으로 추정할 수 있었다.