• 동의생리병리학회지
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• 제22권2호
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• pp.315-320
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• 2008

This study investigated the signaling mechanisms contributed to the vasodilatory effects of HMC05, a herbal prescription. HMC05 acted in an endothelium-independent manner. To elucidate the fundamental mechanisms of its vascular actions, we focused on the signaling molecules involved in actin-myosin filament regulation including 20 kDa myosin light chains (LC20), Rho-associated kinase (ROCK), PKC, JNK and extracellular signal-regulated protein kinase (ERK) in the endothelium-denuded thoracic aorta or isolated smooth muscle cells (SMCs). It lowered the phosphorylation level of LC20 and showed that ROCK, ERK, JNK and $PKC{\alpha}$ pathways played important roles in the effects, as confirmed by the observations with a specific inhibition or activation, and with the activity and the subcellular localization of these molecules. In particular, HMC05 dramatically inhibited the activity of ERK and the downstream signaling of ROCK. It also changed the subcellular localization of the phophorylated $PKC{\alpha}$ as well as the amount of phosphorylation. Taken together, these data indicate that the vascular relaxation effects of HMC05 are attributed to the regulation of these signaling mechanisms.

• 대한한의학회지
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• 제21권1호
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• pp.77-83
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• 2000

This study investigated the effects of Siegesbeckia glabrescens, an antihypertensive remedy, on the contraction evoked by phenylephrine and KCl in isolated rat thoracic arata, and also analyzed antioxidative status in vitro. Siegesbeckia glabrescens revealed dose-dependent relaxation on phenylephrine(PE)/KCl-induced arterial contraction and more markedly on PE-induced contraction. Siegesbeckia glabrescens reduced malondialdehyde(MDA)levels, Phosphatidyl choline-liposome(PC-OOH) contents, linoleic acid-induced lipid peroxidation and exerted 1,1-diphenyl-2- picryl-hydrazyl(DPPH) radical scavenging effect, in vitro. These results indicated that Siegesbeckia glabrescens doesn't relaxe artery through a blocking α-adrenergic receptor and calcium channel mediated by voltage-operated calcium channel, and it s antioxidative effects may be involved in endothelium-dependent relaxation of arteries via vascular protective properites. (J Korean Oriental Med 2000;21(1):77-83)

• 약학회지
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• 제58권4호
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• pp.223-228
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• 2014

The present study was undertaken to investigate the influence of sulforaphane on vascular smooth muscle contractility and to determine the mechanism involved. We hypothesized that sulforaphane, the primary ingredient of broccoli of cruciferous vegetables, plays a role in vascular relaxation through inhibition of Rho-kinase in rat aortae. Intact of denuded arterial rings from male Sprague-Dawley rats were used and isometric tensions were recorded using a computerized data acquisition system. Interestingly, sulforaphane significantly inhibited fluoride, phorbol ester or thromboxane $A_2$ mimetic-induced contraction in denuded muscles suggesting that additional pathways different from endothelial nitric oxide synthesis such as inhibition of Rho-kinase or MEK might be involved in the vasorelaxation. Furthermore, sulforaphane inhibited thromboxane $A_2$-induced increases in pERK1/2 levels suggesting the mechanism including inhibition of thromboxane $A_2$-induced increases in ERK1/2 phosphorylation. This study provides evidence that sulforaphane induces vascular relaxation through inhibition of Rho-kinase or MEK in rat aortae.

• 약학회지
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• 제57권5호
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• pp.376-381
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• 2013

The present study was undertaken to investigate the influence of curcumin on vascular smooth muscle contractility and to determine the mechanism involved. We hypothesized that curcumin, the primary ingredient of Curcuma longa, plays a role in vascular relaxation through inhibition of Rho-kinase in rat aortae. Denuded arterial rings from male Sprague-Dawley rats were used and isometric tensions were recorded using a computerized data acquisition system. Interestingly, curcumin inhibited fluoride-induced contraction but didn't inhibit phorbol ester-induced contraction suggesting that additional pathways different from endothelial nitric oxide synthesis might be involved in the vasorelaxation. Furthermore, curcumin significantly inhibited fluoride-induced increases in pMYPT1 levels. On the other hand, it didn't significantly inhibit phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving inhibition of fluoride-induced MYPT1 phosphorylation. This study provides evidence that curcumin induces vascular relaxation through inhibition of Rho-kinase in rat aortae.

• 약학회지
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• 제58권5호
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• pp.337-342
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• 2014

The present study was undertaken to investigate the influence of diosgenin on vascular smooth muscle contractility and to determine the mechanism involved. We hypothesized that diosgenin, the primary ingredient of Dioscorea villosa, plays a role in vascular relaxation through inhibition of Rho-kinase in rat aortae. Denuded arterial rings from male Sprague-Dawley rats were used and isometric tensions were recorded using a computerized data acquisition system. Interestingly, diosgenin inhibited fluoride-induced contraction but didn't inhibit phorbol ester-induced contraction suggesting that additional pathways different from endothelial nitric oxide synthesis such as inhibition of Rho-kinase might be involved in the vasorelaxation. Furthermore, diosgenin didn't inhibit thromboxane $A_2$-induced increases in pERK1/2 levels suggesting the mechanism excluding inhibition of thromboxane $A_2$-induced increases in ERK1/2 phosphorylation. This study provides evidence that diosgenin induces vascular relaxation through inhibition of Rho-kinase in rat aortae.

• 대한한방내과학회지
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• 제24권2호
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• pp.260-268
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• 2003

Object : This study was undertaken to define the mechanism of GwakHyangJungGiSan-induced relaxation in rabbit common carotid artery contracted by agonists. Method : In order to investigate the effect of GwakHyangJungGiSan on rabbit's contracted vascular ring detached from common carotid artery, vascular ring intact or damaged endothelium was used for the experiment using organ bath. To analyze the mechanism of GwakHyangJungGiSan-induced relaxation, GwakHyangJungGiSan extract was infused into contracted vascular ring which had been pretreated by pretreatment of indomethacin(IM), tetraethylammonium chloride(TEA), $N{\omega}-nitro-L-arginine(L-NNA)$. Result : GwakHyangJungGiSan blocks an inflow of $Ca^{2+}$ and relaxes vascular ring by the action of Nitric oxide from endothelium. Consequently when GwakHyangJungGiSan is prescribed, a rise in blood pressure by the resistance of peripheral vessel may be controlled to some extent and so it is anticipated that hypertension, a disorder of blood flow from the vascular contraction and vascular disease will be treated well.

• 동의생리병리학회지
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• 제29권6호
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• pp.492-497
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• 2015

In the present study, vasorelaxant effect of the extract of seeds of Oenothera odorata (SOO) and its possible mechanism responsible for this effect were examined in vascular tissues isolated from rats. Changes in vascular tension, 3',5'-cyclic monophosphate (cGMP) levels were measured in thoracic aorta rings from rats. Methanol extract of seeds of Oenothera odorata relaxed endothelium-intact thoracic aorta in a dose-dependent manner. A dose-dependent vascular relaxation was also revealed by treatment of ethylacetate, n-butanol, and H₂O (aqua extract of seeds of Oenothera odorata , ASOO) extracts partitioned from methanol, but not by hexane extract. However, the vascular relaxation induced by ASOO were abolished by removal of endothelium of aortic tissues. Pretreatment of the endothelium-intact vascular tissues with N^G-nitro-L-arginine methyl ester (L-NAME) or ¹H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1- one (ODQ) significantly inhibited vascular relaxation induced by ASOO. Moreover, incubation of endothelium-intact aortic rings with ASOO increased the production of cGMP. However, ASOO-induced increases in cGMP production were blocked by pretreatment with L-NAME or ODQ. The vasorelaxant effect of ASOO was attenuated by tetraethylammonium (TEA), 4-aminopyridine, and glibenclamide attenuated. On the other hand, the ASOO-induced vasorelaxation was not blocked by verapamil, and diltiazem. Taken together, the present study demonstrates that ASOO dilate vascular smooth muscle via endothelium-dependent NO-cGMP signaling pathway, which may be closely related with the function of K⁺ channels.

• The Korean Journal of Physiology and Pharmacology
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• 제20권5호
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• pp.539-545
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• 2016

Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function.

• 생명과학회지
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• 제13권5호
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• pp.634-641
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• 2003

외부에서 가해진 비소 스트레스가 내피유무에 따른 흰쥐 대동맥의 수축력 증가와 이완반응에 미치는 영향을 알아보고자 본 실험을 실시하였다. 혈압의 측정은 생리기록계를 이용하였고, 내피 유무에 따른 혈관의 수축력은 Organ bath에 조직을 걸고 자동조절 생리기록계를 이용하여 측정하였다. 중추신경계를 파괴시킨 흰쥐의 생체 내 실험에서 비소처리로 vasopressin과 phenylephrine에 의한 혈관 수축력은 대조군에 비해 각각 19.1%와 46.6%로 대동맥의 혈압은 상승되었다. 0, 0.5, 1, 2 및 4 mM As을 처리한 적출 대동맥 실험에서 phenylephrine $(10^{-6}M)$을 가했을 때 5시간까지는 혈관 수축력의 변화가 미미했으나 8시간째 비소 처리군은 대조군에 비해 39% 증가된 값을 보여 수축력이 더욱 유의하게 증가되었다. 내피 제거 시 저농도 비소처리에서 다소 신속한 수축반응을 보였으나 고농도 비소 처리시에는 내피유무에 따른 차이가 유의적이지 않았다. 이완제 sodium nitroprusside와 acetylcoline를 처리했을 때 대조군에 비해 다소 증가된 이완력을 보였고, 시간경과에 따라 내피 비의존적인 nitroprusside와 달리 내피 의존적인 acetylcholine에서 이완력이 대조군에 비해 다소 촉진되었다. 이상의 결과에서 4 mM As처리시 혈관의 수축력은 증가되었으나 내피유무에 따른 차이는 유의적이지 않았고, 내피가 혈관의 이완력을 다소 촉진시킨 것으로 나타났다. 결론적으로 비소처리한 혈관은 내피유무와 무관하게 수축력이 증가되어 장기간 고농도 비소에 노출 시 고혈압을 유발할 우려가 있을 것으로 여겨진다.

• Journal of Chest Surgery
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• 제34권7호
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• pp.515-523
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• 2001

배경: 당뇨병 환자에서 사망률과 이환률의 원인은 70%이상 혈관계의 합병증에 기인한다. 이러한 합병증은 혈관 내피세포 이완 작용 이상과 연관되어 있으며 이는 oxygen free radical의 직접적인 독성으로 추정되어 본 연구는 당뇨를 유발시킨 백서 복부 대동맥 운동성에 대한 Vit C의 보호효과를 연구 목적으로 한다. 대상 및 방법: 백서 60마리를 실험군(n=33)과 대조군(n=27)으로 나누고 실험 군은 streptozotocin을 투여하여 당뇨를 유발시켰다. 각각 실험 군과 대조군을 ascorbic acid를 투여한 군과 투여하지 않은 군으로 세분한 후 ascorbic acid투여 직후, 6주, 9주, 12주후의 복부 대동맥 혈관근육의 운동성을 측정하였다. 결과: 대조군의 경우 6주째 복부 대동맥 절편에서 acetylcholine투여 후 정상적인 이완반응이 나타났으나 실험군의 경우 현저히 저하됨이 관찰되었다. 9, 12주 째 절편에서는 실험군 중 ascorbic acid투여군에서 acetylcholine에 의한 이완반응이 거의 대조군에서의 결과와 일치할 정도로 회복되었다. 결론: 이상의 결과로 당뇨병을 유발한 백서에서 내피세포 의존적인 장애가 나타남을 확인할 수 있었으며 이러한 장애는 ascorbic acid의 투여로 회복됨을 알 수 있었으며 그 효과는 항산화 작용에서 비롯된 것으로 생각되므로 ascorbic acid가 당뇨환자의 혈관성 질환에 대해 보호적 효과를 보일 수 있을 것으로 사료된다.