• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제5권1호
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• pp.87-92
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• 2001

Carbon monoxide (CO) binds to soluble guanylate cyclase to lead its activation and elicits smooth muscle relaxation. The vascular tissues have a high capacity to produce CO, since heme oxygenase-2 (HO-2) is constitutively expressed in endothelial and smooth muscle cells, and HO-1 can be greatly up-regulated by oxidative stress. Moreover, the substrate of HO, heme, is readily available for catalysis in vascular tissue. Although the activation of heme oxygenase pathway under various stress conditions may provide a defence mechanism in compromised tissues, the specific role of HO-1-derived CO in the control of aortic contractility still remains to be elucidated. The present study was done to determine the effect of HO-1 induction on the aortic contractility. Thus, the effects of incubation of aortic tissue with S-nitroso-N-acetylpenicillamine (SNAP) for 1 hr on the aortic contractile response to phenylephrine were studied. The preincubation with SNAP resulted in depression of the vasoconstrictor response to phenylephrine. This effect was restored by HO inhibitor or methylene blue but not by NOS inhibitor. The attenuation of vascular reactivity by preincubation with SNAP was also revealed in endothelium-free rings. $AlF4^--evoked$ contraction in control did not differ from that in SNP-treated group. These results suggest that increased production of CO was responsible for the reduction of the contractile response to phenylephrine in aortic ring preincubated with SNAP and this effect of SNAP was independent on endothelium.

• 대한약리학회지
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• 제26권2호
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• pp.135-144
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• 1990

Propylthiouracil(PTU)을 4주 및 12주간 투여한 흰쥐의 대동맥을 적출하여 혈관수축제와 이완제에 대한 반응을 관찰하여 다음과 같은 결과를 얻었다. PTU를 처치한 실험군에서는 대조군에 비해 현저한 체중저하와 혈중 갑상선호르몬의 감소를 보였다. PTU를 처치한 흰쥐의 대동맥에 대한 norepinephrine (NE)과, calcium및 potassium 이온에 의한 최대수축 반응은 대조군에 비하여 유의하게 감소되었다. 그러나 NE에 대한 중간유효량은 증가되었으나, calcium이온에 대한 중간 유효량은 유의한 차이가 없었다. 그리고 acetylcholine, histamine, isoproterenol 및 nitroprusside에 의한 대동맥의 이완작용은 대조군에 비해 증가된 경향을 보였다. PTU를 12주간 처치한 군에 있어서 acetylcholine에 의한 최대 이완반응은 대조군에 비해 유의하게 증가되었지만 다른 이완제에 의해서는 유의한 차이가 없었다. PTU를 4주간 처치한 군에 있어서는 대조군에 비하여 혈관이완제에 대한 중간억제량은 유의한 차이가 없었지만, 12주 처치군에 있어서는 isoproterenol 및 nitroprusside에 대한 중간억제량은 감소 되었으나 acetylcholine 및 histamine에 대한 중간억제량은 유의한 차이가 없었다. 이상의 결과로 미루어 보아 PTU-처치에 의한 혈관 반응성의 변화는 혈관 내피세포보다는 혈관 평활근세포자체의 변화에 기인되며, 이러한 세포내의 변화는 갑상선 기능이 저하된 후에도 계속되고 있음을 알 수 있었다.

• 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)

• 대한한의학회지
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• 제18권2호
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• pp.15-32
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• 1997

This study was undertaken to define the mechanism of Siegesbeckiae Herba-induced relaxation in rabbit common carotid artery contracted by agonists. In order to investigate the effect of Siegesbeckiae Herba on contracted rabbit carotid arterial strips, transverse strips with intact or damaged endothelium were used for the experiment using organ bath. To analyze the mechanism of Siegesbeckiae Herba-induced relaxation, Siegesbeckiae Herba extract infused into contracted arterial strips induced by agonists after treatment of lanthanum chloride, indomethacin, atropine, $N\omega-nitro-{_L}-arginine$, cobalt chloride or methylene blue. The relaxation effect of Siegesbeckiae Herba was dependent on the presence of endothelium, showing that Siegesbeckiae Herba-induced relaxation was not observed in the strips without endothelium. The endothelium-dependent relaxation induced by Siegesbeckiae Herba was suppressed by the pretreatment of lanthanum chloride, $N\omega-nitro-{_L}-arginine$, cobalt chloride or methylene blue, but it was not observed in the strips pretreated with indomethacin or atropine. These results demonstrated that Siegesbeckiae Herba may inhibit agonist-induced contraction through an increase in the cyclic GMP by the production of nitric oxide in the vascular endothelial cells.

• 대한약침학회지
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• 제6권3호
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• pp.49-55
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• 2003

This study was undertaken to define the effect of ChungSangSaWhaTang on the norepinephrine-induced arterial contraction and the mechanism of ChungSangSaWhaTang-induced relaxation. In order to investigate the effect of ChungSangSaWhaTang on contracted rabbit carotid arterial strips, transverse strips with intact or damaged endothelium were used for the experiment using organ bath. To analyze the mechanism of ChungSangSaWhaTang-induced relaxation, ChungSangSaWhaTang extract infused into contracted arterial strips induced by norepinephrine after treatment of indomethacin, $N_{\omega}$-nitro-L-arginine, or tetraethylammonium chloride. ChungSangSaWhaTang relax arterial strip with endothelium contracted by norepinephrine, but in the strips without endothelium, ChungSangSaWhaTang-induced relaxation was significantly inhibited. The endothelium-dependent relaxation induced by ChungSangSaWhaTang was decreased by the pretreatment of $N_{\omega}$-nitro-L-arginine, but it was not observed in the strips pretreated with indomethacin or tetraethylammonium chloride. We suggest that ChungSangSaWhaTang may inhibit agonist-induced contraction through the formation of nitric oxide in the vascular endothelial cells.

• 대한수의학회지
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• 제44권3호
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• pp.357-366
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• 2004

We studied the effect of propofol (PPF) on the endothelium-dependent vascular responses in isolated rat thoracic aorta. In aortic rings with endothelium, PPF inhibited the phenylephrine (PE)-induced contraction in a concentration-dependent manner. In PE-precontracted preparations, PPF attenuated the endothelium-dependent relaxation by acetylcholine but not by A23187. And PPF did not attenuate the endothelium-independent relaxation by sodium nitroprusside (SNP). The relaxation induced by acetylcholine in PE-precontracted aortic rings was significantly augmented by zaprinast, a cGMP-specific phosphodiesterase inhibitor, and this augmentation was inhibited by PPF. Although SNP-induced relaxation was significantly augmented by zaprinast, this augmentation was not inhibited by PPF. In preparations preconstricted with PE, the PPF-induced relaxation was inhibited by atropine. In addition, PPF attenuated the vasorelaxation by phosphodiesterase inhibitors (IBMX, Ro20-1724 or zaprinast except milrinone). In vivo, the infusion of acetylcholine and SNP showed decreased arterial blood pressure in rats. The pre-injection of PPF inhibited the acetylcholine-induced blood pressure lowering, but not the SNP-induced blood pressure lowering. These results suggest that PPF can attenuate in part the acetylcholine-induced vasorelaxation and blood pressure lowering through the inhibition of the acetylcholine receptor-mediated endothelium-derived relaxing factor by acting on endothelium. It is considered that the inhibitory effect of PPF on the vasorelaxation is due to the decreased level of cGMP which can be attributed to the inhibition of the muscarinic receptor and/or receptor-G-protein interaction.

• 동의생리병리학회지
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• 제19권3호
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• pp.797-801
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• 2005

While conducting an in vitro screening of various medicinal plant extracts, an aqueous extract of Rosa rugosa Radix (ARR) was found to exhibit a distinct vasorelaxant activity. ARR induced a concentration-dependent relaxation of the phenylephrine-precontracted aorta. This effect disappeared with the removal of functional endothelium. Pretreatment of the aortic tissues with NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]-oxadiazole-[4,3-]-quinoxalin-1-one (ODQ) completely inhibited the relaxation induced by ARR. ARR-induced vascular relaxations were also markedly attenuated by addition of diltiazem or verapamil. However, the relaxant effect of ARR was not blocked by pretreatment with indomethacine, tetraethylammonium (TEA), glibenclamide, atropine, or propranolol. Taken together, the present study suggests that ARR dilates vascular smooth muscle via endothelium-dependent NO/cGMP signaling.

• Nutritional Sciences
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• 제8권3호
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• pp.153-158
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• 2005

Numerous natural herbal compounds have been reported to inhibit adhesion and migration of leukocytes to the site of inflammation Licorice extracts, which have been widely used in traditional Chinese medicinal preparation, possess various pharmacological effects. Isoliquiritigenin, a biogenetic precursor of flavonoids with various pharmacological effects, is a natural pigment present in licorice. We attempted to explore whether licorice extracts and isoliquiritigenin mitigate monocyte adhesion to tumor necrosis factor-$\alpha$ (TNF-$\alpha$)-activated human umbilical vein endothelial cells (HUVEC). In addition, it was tested whether the inhibition of monocyte adhesion to the activated HUVEC accompanied a reduction in vascular cell adhesion molecule-l expression(VCAM-l). Dry-roasted licorice extracts in methylene chloride but not in ethanol markedly interfered with THP-l monocyte adhesion to INF-$\alpha$-activated endothelial cells. licochalcone A compound isolated from licorice extract in methylene chloride appeared to modestly inhibit the interaction of THP-l monocytes and activated endothelium. In addition, isoliquiritigenin abolished the monocyte adhesion with attenuating VCAM-l protein expression on HUVEC induced by INF-$\alpha$. These results demonstrated that non-polar components from dry-roasted licorice extracts containing licochalcone A as well as isoliquiritigenin were active in blocking monocyte adhesion to cytokine-activated endothelimn, which appeared to be mediated most likely through the inhibition of VCAM-l expression on HUVEC. Therefore, licorice may hamper initial inflammatory events on the vascular endothelium involving induction of endothelial cell adhesion molecules.

• 대한수의학회지
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• 제43권4호
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• pp.615-624
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• 2003

Vascular smooth muscle relaxation is modulated by an increase in cGMP subsequent to nitric oxide (NO) production by endothelial cells. The effects of cAMP and cGMP phosphodiesterase (PDE) inhibitors were investigated in phenylephrine-precontracted rat aorta rings by using the specific inhibitors of PDE I, III, IV and V as relaxing agents (calmodulin-activated PDE inhibitors, IBMX and $W_7$, type I; cAMP-specific PDE inhibitors, milrinone, type IV; Ro 20-1724, type III and cGMP-specific PDE inhibitor, zaprinast, type V). All the PDE inhibitors produced a concentration-dependent relaxation in the ring with intact endothelium (+E). Except for milrinone, all the PDE inhibitors-induced relaxations were inhibited by removal of extracellular $Ca^{2+}$, $N^G$-nitro-L-arginine, $N^G$-nitro-L-arginine methyl ester, methylene blue (MS) or nifedipine. The specific PDE I and PDE IV inhibitors both produced endothelium-independent relaxations which were inhibited by MS in -E rings. However, zaprinast had no effect in -E rings. Except for milrinone, sodium nitroprusside (a NO donor)-induced relaxation was significantly augmented by all PDE inhibitors in +E rings. The results suggest that I) the vasorelaxant properties of IBMX, $W_7$, Ro 20-1724 and zaprinast are dependent on endothelium or on interaction with $Ca^{2+}$ regulation, 2) each PDE is differently distributed in vascular tissues (endothelial and smooth muscle cells), 3) the vasodilations of PDE inhibitors are due to the increase of cAMP and cGMP formation through inhibition of cAMP- and cGMP-PDE and 4) the vasodilation action of milrinone does not involve in endothelial-cyclic nucleotide system.