• Experimental and Molecular Medicine
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• 제50권12호
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• pp.11.1-11.9
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• 2018

Estrogen has diverse effects on cardiovascular function, including regulation of the contractile response to vasoactive substances such as serotonin. The serotonin system recently emerged as an important player in the regulation of vascular tone in humans. However, hyperreactivity to serotonin appears to be a critical factor for the pathophysiology of hypertension. In this study, we examined the modulatory mechanisms of estrogen in serotonin-induced vasoconstriction by using a combinatory approach of isometric tension measurements, molecular biology, and patch-clamp techniques. $17{\beta}$-Estradiol (E2) elicited a significant and concentration-dependent relaxation of serotonin-induced contraction in deendothelialized aortic strips isolated from male rats. E2 triggered a relaxation of serotonin-induced contraction even in the presence of tamoxifen, an estrogen receptor antagonist, suggesting that E2-induced changes are not mediated by estrogen receptor. Patch-clamp studies in rat arterial myocytes showed that E2 prevented Kv channel inhibition induced by serotonin. Serotonin increased Src activation in arterial smooth muscle required for contraction, which was significantly inhibited by E2. The estrogen receptor-independent inhibition of Src by E2 was confirmed in HEK293T cells that do not express estrogen receptor. Taken together, these results suggest that estrogen exerts vasodilatory effects on serotonin-precontracted arteries via Src, implying a critical role for estrogen in the prevention of vascular hyperreactivity to serotonin.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.503-516
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• 2020

KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC₅₀, the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the β ancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQ-specific agonist in the tissue.

• Journal of Yeungnam Medical Science
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• 제28권2호
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• pp.165-172
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• 2011

Gastric glomus tumor is a rare mesenchymal tumor that originates from modified smooth muscle cells of the glomus body. Glomus tumors are commonly observed in peripheral soft tissue, such as dennis or subungal region, but rarely in the gastrointestinal tract. A 39-year-old woman was admitted due to epigastric soreness. Upper gastrointestinal endoscopy revealed a subepithelial mass measuring 3.5 cm with central ulceration at the lesser curvature-posterior wall of the antrum. Characteristically, contrast enhanced abdominal computed tomography scan demonstrated high enhancement of the submucosal mass up to the same level of the abdominal aorta in the arterial phase; this enhancement persisted to delayed phase. Due to the risk of bleeding and malignancy, wedge resection of the submucosal tumor was performed. Histologic findings were compatible with a glomus tumor.

• 약학회지
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• 제51권5호
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• pp.301-306
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• 2007

Rosiglitazone ($Avandia^{(R)}$) represents a new class of antidiabetic drugs which are $PPAR{\gamma}$ agonists. The present study was undertaken to determine whether the new antidiabetic rosiglitazone influences on the agonist-induced regulation of vascular smooth muscle contraction as an antihypertensive and, if so, to investigate the related mechanism. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Rosiglitazone decreased Rho-kinase activating agonist (NaF or thromboxane $A_2$ mimetic)-induced contraction but not depolarization- or phorbol ester-induced contraction. Surprisingly, it slightly potentiated the latter contraction possibly opening a voltage-dependent calcium channel by its chemical structure on 50 mM KCI- or $1{\mu}M$ phorbol 12,13-dibutyrate-induced vasoconstriction. In conclusion, this study provides the evidence and possible related mechanism concerning the biphasic effect of an antidiabetic rosiglitazone as a possible antihypertensive on the agonistinduced contraction in rat aortic rings regardless of endothelial function.

• 대한의생명과학회지
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• 제8권4호
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• pp.257-268
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• 2002

Chronic infection and inflammation have recently been implicated as important etiologic agents of atherosclerosis. Several agents have been suggested as possible candidates including cytomegalovirus (CMV), herpes simplex vims type 1 (HSV-1), Epstein-Barr virus (EBV), Chlamydia pneumoniae, and Helicobacter pylori. We evaluated the relationship between cytornegalovirus infection and atherosclerosis by in situ hybridization and polymerase chain reaction (PCR). We examined 23 subjects with atherosclerosis and 10 matched control subjects without atherosclerosis. CMV was detected by in situ hybridization in 60.9% (14/23) of aorta and 42.9% (9/21) of coronary arteries in subjects with atherosclerosis. It was also detected by PCR in 65.2% (15/23) of aorta and 52.4% (11/21) of coronary arteries. CMV was detected on areas showing early or advanced atheromatous changes. Cells morphologically identical to smooth muscle cells, endothelial cells, lymphocytes, fibroblasts, and Schwann cells were positively reacted with the CMV probe. However. none of the cells to which the probe hybridized contained inclusion bodies, thus strongly suggesting that the arterial wall may be a site of CMV latency. This result Indicates that CMV may potentially play a direct or indirect role in the pathogenesis of human atherosclerosis.

• 약학회지
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• 제55권2호
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• pp.138-144
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• 2011

The aim of present study was to investigate the possible influence and related mechanism of resveratrol on U-46619 (high concentration)-induced vasoconstriction. Agonist-induced vascular smooth muscle contractions involve the activation of thick or thin filament pathway. However, there are no reports addressing the question whether this pathway is involved in resveratrol-induced relaxation in rat aortae contracted with high U-46619. We hypothesized that MEK or Rho-kinase inhibition plays a role in vascular relaxation evoked by resveratrol in rat aortae. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Resveratrol fully inhibited U-46619 in low concentration-induced contraction regardless of endothelial function. However, resveratrol partially decreased U-46619 in high concentration-induced contraction regardless of endothelial function. Interestingly, only in U-46619 (high concentration)-induced contraction, no significant decrease was observed in phospho-ERK1/2 levels and slight decrease in phospho-MYPT1 levels suggesting that additional pathways different from them or endothelial nitric oxide synthesis might be involved in the vasorelaxation. In conclusion, in high U-46619-contracted rat aortae, resveratrol showed relaxation response regardless of endothelial function significantly but slightly decreasing MYPT1 phosphorylation rather than ERK1/2 phosphorylation.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제23권1호
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• pp.1-6
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• 2001

Purpose : This study was undertaken to observe the occurrence of the vessel aneurysms according to several different methods of microvascular anastomosis. Mterials & methods : Forty Sprague-Dawley rats, weighing $180{\sim}200$ grams, were used for this experiment. The rats were divided into 4 groups. Group 1 (10 rats): The adventitia was trimmed off 5mm from the cut edge each and 20 arterial anastomoses were performed using 8 to 10 interrupted 9-0 polypropylene ($Prolene^{TM}$, Ethicon, U.K.) suture. Group 2 (10 rats): The adventitia was trimmed off as in group 1. Twenty arterial anastomoses were performed using continuous 9-0 polypropylene($Prolene^{TM}$, Ethicon, U.K.) suture. Group 3 (10 rats): The adventitia was stripped only 1mm from the cut edge each but not removed,. Twenty arterial anastomoses were performed using 8 to 10 interrupted 9-0 polypropylene($Prolene^{TM}$, Ethicon, U.K.) suture. Group 4 (10 rats): The adventitia was handled as in group 3. Twenty arterial anastomoses were performed using 9-0 polypropylene($Prolene^{TM}$, Ethicon, U.K.) suture. The arteries of the animals in all groups were explored at 28th days. We examined patency, presence of an aneurysm, other vascular abnormalities and microscopically observed the aneurysms with H&E and Van-Gieson stains. Result : 1. Patency rate was 80% in group 1, 95% in group 2, 85% in group 3 and 90% in group 4, respectively. 2. Aneurysm occurred 20% in group 1, 5% in group 2, 5% in group 3 and 5% in group 4, respectively. 3. There was no other vascular abnormalities in each group. 4. Infection rate was 5% in group 1, 0% in group 2, 20% in group 3 and 15% in group 4, respectively. 5. In the histopathological findings, we observed partially necrotic changes, loss and fragmentation of outer elastic lamella of smooth muscle in media and the proliferation of hyperplastic subintima. A lot of inflammatory cells were infiltrated in hyperplastic intima. Conclusions : On the basis of these observation, we could state that there were little differences in the occurrence of aneurysms according to different anastomotic suture methods.

• Nutrition Research and Practice
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• 제13권4호
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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.

• The Korean Journal of Physiology
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• 제16권1호
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• pp.1-11
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• 1982

Force development of smooth muscle cells is directly regulated by the concentration of free calcium ions in the sarcoplasm, and the sarcoplasmic concentration of calcium ion can be modulated by electrogenic Na-K pump. The role of Na-K pump on vascular tone was studied in isolated rabbit renal artery. Helical strips of arterial muscle were prepared from left renal arteries. All experiments were performed in $HCO_3^--buffered$ Tyrode solution which was aerated with $3%CO_2-97%\;O_2$ mixed gas and kept at $35^{\circ}C$. In some experiments, rabbit was injected intraperitoneally $18{\sim}24$ hours prior to the experiments, with a large dose(5 mg/kg body wt) of reserpine, in order to eliminate the catecholamines present in intrinsic adrenergic nerve terminate. Treatment used in this experiment that inhibits Na-K pump was the exposure of strips to K-free Tyrode solution. Contractile response to K free Tyrode solution developed slowly and the time required for maximum contracture was $20{\sim}30$ minutes. This K-free contracture was rapidly relaxed by the addition of potassium to the bathing solution. No K-free contracture occurred in a Ca-free Tyrode solution. But contraction developed rapidly when calcium ion was added to the bathing solution after 30 minute exposure of the strip to Ca-free Tyrode solution. This contracture was completely inhibited by Ca-antagonist, verapamil. The K-free contracture was abolished by ${\alpha}-adrenergic$ blocker, phentolamine, as well as by the catecholamine depletion from adrenergic nerve terminals. Even in reserpinized strip, the exogenous norepinephrine-induced contraction in K-free Tyrode solution was rapidly suppressed by the addition of potassium ion. The results of this experiment suggest that K free contracture develops by norepinephrine release from adrenergic nerve terminals, while the relaxation of K-free contracture is induced by the activation of electrogenic Na-K pump.

• 대한약리학회지
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• 제15권1_2호
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• pp.29-37
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• 1979

Cd 중독(中毒)으로 가토(家兎)에 고혈압(高血壓)을 일으키고 이를 중독(中毒) 가토(家兎)와 대조(對照) 비중독(非中毒) 가토(家兎)의 간문맥(肝門脈), 흉부(胸部) 대정맥(大動脈) 및 폐정맥(肺動脈)을 적출하여 in vitro에서 장력(張力)-길이의 관계를 관찰하고 NE, $K^+$-depolariration 및 angiotensin의 수축(收縮) 효과(效果)를 비교(比較)하였다. 1. 비중독(非中毒) 대조군의 평균 동맥압은 $87.0{\pm}4.7mmHg$이었고 Cd 중독군(中毒群)에서는 $109.0{\pm}2.8mmHg$로 Cd 중독(中毒)에 의하여 의의(意義)있는 증가(增加)를 나타내었다. 2. 동(動) 정맥(靜脈)의 장력(張力)-길이 곡선(曲線)에서 Cd 중독(中毒) 가토의 간문맥(肝門脈)은 passive tension의 증가에 따라 distensibility가 현저히 증가되나 대동맥(大動脈)에 있어서는 오히려 대조군에 비(比)하여 유의(有意)한 감소(減少)를 나타내었고 폐동맥(肺動脈)은 아무런 차이(差異)를 나타내지 아니하였다. 3. Passive tension의 증가에 따른 active tension의 변화(變化)는 대동맥(大動脈)에 있어서는 Cd중독으로 현저히 감약되었으나 간문맥(肝門脈)이나 폐동맥(肺動脈)은 대조군과 별다른 차이(差異)가 없었다. 4. Cd 중독군(中毒群)이나 비중독(非中毒) 대조군에서 passive tension의 변동에 따른 수축결과(收縮效果)는 세 혈관에서 모두 유의(有意)한 차이를 나타내지 아니하였다. 5. 대동맥(大動脈) 절편에 대한 angiotensin의 수축(收縮) 효과(效果)는 Cd 중독군(中毒群)에서 유의하게 저하되었다.