• 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.

• 동의생리병리학회지
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• 제18권1호
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• pp.69-74
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• 2004

We have examined the relaxative response to the water extract of Rheum undulatum L. (ERU) and water extract of alcohol steamed Rheum undulatum L. (SRU) with isolated thoracic aorta from sprague dawley (SD) rat. Rat thoracic aorta was investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to ERU and SRU were investigated in vessels precontracted with 5-hydroxytryptamine(5-HT). We found that the thoracic aorta segments responded to ERU and SRU with a dose-dependent vasorelaxation : The thoracic aorta segments responded to ERU and SRU with a dose-dependent vasodilation. The amounts of emodin were 0.063%, 0.076% and 0.145% in ERU and SRU, respectable. The 5-HT induced contraction at 10-4M were inhibited by 85.2±4.76% and 84.0±2.91% after addition of the 0.1mg/mL water extract of ERU and SRU. The 5-HT induced contraction at 10/sup -3/M were inhibited by 100% after 10/sup -3/M emodin. In conclusion, vasodilation effect of the water extract of Rheum undulatum L. in rat thoracic aorta was not decreased according to the processing of alcohol steamed Rheum undulatum L.

• Biomolecules & Therapeutics
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• 제11권2호
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• pp.133-138
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• 2003

The vascular relaxant and antihypertensive effects of newly developed salts of amlodipine-maleate and camsylate-were evaluated on isolated aorta from rats and in spontaneously hypertensive rats, and compared with those of amlodipine besylate, a standard drug. Amlodipine besylate concentration-dependently inhibited $Ca^{2＋}$-induced contraction in depolarised rat aorta($IC_{50}$/: 4.17 nM), with a very slow onset of action. Amlodipine maleate and amlodipine camsylate also showed vascular relaxant effect with a pattern and a potency similar to those of amlodipine besylate($IC_{50}$/: 3.62 and 3.28 nM, respectively). Amloclipine besylate produced a dose-dependent and long-lasting(>10∼24h) antihypertensive effect with a slow onset of action (ED$_{20}$: 2.31 mg/kg) in spontaneously hypertensive rats. Amlodipine maleate and amlodipine camsylate also exerted antihypertensive effects with a pattern and a potency similar to those of amlodipine besylate(ED$_{20}$: 2.09 and 2.21 mg/kg, respectively). These results suggest that amlodipine maleate and amlodipine camsylate are not statistically differ with amlodipine besylate in relaxant effect of $Ca^{2＋}$-induced contraction in depolarised rat aorta and in antihypertensive effect in spontaneously antihypertensive rats.

• 동의생리병리학회지
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• 제16권5호
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• pp.938-942
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• 2002

We have examined the relaxational response to the water extract of Rheum palmatum L.(ERP) and water extrc alcohol processed Rheum palmatum L.(ARP) in isolated thoracic aorta from sprague dawley (SD) rat. Rat thoracic aort investigated in vessel segments suspended for isometric tension recording by polygraph. Responses to ERP and ARP investigated in vessels precontracted with 5-hydroxytryptamine(5-HT). We found that the thoracic aorta segments respo to ERP and ARP with a dose-dependent vasorelaxation. We found that ; The thoracic aorta segments responded to I and ARP with a dose-dependent vasodilation. The 5-HT induced contraction at 10/sup -4/M were inhibited by 71.7% and a: after addition of the 0.01 g/mL water extract of ERP and ARP. The 5-HT induced contraction at 10/sup -4/M were inhibite 100% after 10/sup -3/M emodin. The concentration of emodin was 0.027% and 0.098% in ERP and ARP. In condusion, ERP ARP induced relaxation in the isolated rat thoracic aorta were composed of dose-dependent relaxation. and it has pi vasodilation.

• 약학회지
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• 제34권3호
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• pp.180-191
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• 1990

A comparison was made of the effects of selective ${\alpha_1}-adrenoceptor$ agonist phenylephrine and selective ${\alpha_2}-adrenoceptor$ agonist clonidine on endothelium-containing and endothelium-denuded rings of the rat aorta. In the case of phenylephrine, removal of endothelium increased sensitivity 2.5 fold at $EC_{50}$ level and maximum contractive response 1.4 fold. In the case of clonidine, which gave only 15% of maximum contractive response given to phenylephrine on endothelium-containing rings, removal of the endothelium increased sensitivity 5.6 fold at $EC_{50}$ level and maximum contractive response 5 fold, which was about 55% of that given by phenylephrine. In endothelium-denuded ring, phenylephrine-induced contraction tended to be more increased in tonic contraction than in phasic contraction as compared to that in endothelium-containing ring, while clonidine-induced contraction was monophasic and was increased only in tonic contraction. In the calcium-free solution or in the presence, of verapamil, contraction stimulated by clonidine was almost abolished while that stimulated by phenylephrine produced only phasic contraction. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium derived relaxing factor (EDRF), because hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent relaxation was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in 5-hydroxytryptamine-precontracted ring even when its contractile action was blocked by the ${\alpha_1}-adrenoceptor$ antagonist, prazosin. When the efficacy of phenylephrine was reduced to about the initial efficacy of clonidine by pretreatment with dibenamine, the contraction-response curves for phenylephrine became very similar to the corresponding curves obtained for clonidine before receptor inactivation. In the dibenamine-treated rings, contraction of phenylephrine was abolished in calcium-free solution or in the presence of verapamil like that obtained for clonidine before receptor inactivation. These results suggest that EDRF spontaneously released from endothelium depress contraction more profoundly in a case of an agonist with low efficacy and the phenylephrine-induced contraction was totally dependent on extracellular calcium as was that obtained for clonidine when the efficacy of phenylephrine was reduced to that of clonidine by irreversible inactivation of ${\alpha_1}-adrenoceptor$ with dibenamine.

• Biomolecules & Therapeutics
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• 제9권2호
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• pp.119-124
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• 2001

In order to determine the role of dehydroepiandrosterone (DHEA), the important sex-steroid hormone precursor, in vascular reactivity in rats, animals were treated for two weeks with DHEA or sex hormones, and the vascorelaxant and contractile responses of isolated aorta were examined. DHEA diminished the acetylcholine (ACh)-induced relaxation in female rats, while the drug was without effect in males. Testoterone lowered the vasorelaxant activity to ACh in either sex. 17$\beta$-Estradiol enhanced ACh-induced vasorelaxation in male rats, but this female sex hormone did not influence in females. In male rats, the androgen receptor antagonist flutamide also enhanced vasorelaxant action of ACh. When the male rat aorta was incubated in vitro with a nitric oxide (NO) synthase inhibitor L-NAME, phenylephrine-induced contraction was greatly potentiated in DHEA-pretreated rats compared to control ones. The present results suggest that DHEA stimulates mainly androgen in female, but both androgen and estrogen in male rats. The participation of NO In the modulation of vascular reactivity with pretreated DHEA was also considered.

• 동의생리병리학회지
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• 제19권5호
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• pp.1311-1316
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• 2005

This study was designed to potentiate the vasodilation effect of Banhabackchulchunma-Tang(BCT) prescription by change of mixture. Six different BCT compositions were made according to mixture of herbs. The vascular relaxation effects of 6 different BCT compositions were examined on phenylephrine(PE)-precontracted rat thoracic aorta. The BCT-1 composition exerted significant relaxation on phenylephrine- or KCI- contracted rat thoracic aorta. Its elaxation was endothelium- independent in both PE- and KCl-induced contraction. Treatment of glibenclamide or tetraethylammonium(TEA) did not affect the relaxation of BCT-1. Vasorelaxation efficacy of BCT-1 was also not influenced by low (25mM) or high (50mM, 80mM) KCl-induced contraction. Furthermore, the contraction by increasing $Ca^{2+}$ concentrations (0.3-10.0mM) to a $Ca^{2+}$-free high K+ (60mM) was significantly reduced by pretreatment with BCT-1 In addition, the relaxant effects were not inhibited by pretreatment of rat aorta with L-NAME, MB, indomethacin and atropine. These results confirm that BCT-1 may exerts its vasodilation effect by endothelium-independent manner. According to the above results, we suggest that the relaxation effect of BCT-1 is endothelium-independent and is related with block of $Ca^{2+}$ influx via $Ca^{2+}$ channel.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.185-195
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• 2000

Vascular diseases are significant complications of diabetes mellitus (DM), and the endothelial cells may play a pivotal role in the development of vascular disease in DM. Endothelin-1 (ET-1) released from endothelium is a potent vasoconstrictor peptide and circulating level of ET-1 is increased in a variety of disease states. The purpose of this study was to determine the changes of responsiveness to ET-1 in DM, and we experimented on the changes in the ET-1-induced contraction, levels of nitrite and lipid peroxidation, and ET-1 immunoreactivity in aorta from streptozotocin-induced DM rats. DM was induced by single injection of streptozotocin (55 mg/kg, i.p.). The immunoreactive ET-1 levels in endothelial layer of thoracic aorta were much higher in DM rats than control rats. Nitrite in tissue homogenate was decreased and plasma nitrite was increased in DM rats. Malondialdehyde (MDA) was significantly increased in DM rats and cGMP was not significantly different between control and DM rats. ET-1 produced concentration- dependent contractile responses that are significantly attenuated in DM rats compared to controls. In the presence of selective $ET_A$ receptor antagonist BQ610, the maximum contraction was decreased and the concentration ratios for BQ610 yielded $pA_2$ values of 7.3 (slope, 0.65) in control rats, whereas BQ610 had no antagonistic effect on ET-1-induced contraction in DM rats. However, pretreatment with BQ788, an $ET_B$ receptor antagonist, maximum response was decreased and the dose-response curves for ET-1 were shifted to the right in both groups and $pA_2$ values were 7.9 and 7.7 (slope, 1.05 in control and DM rats), respectively. IRL 1620 and sarafotoxin S6c, $ET_B$ agonists, induced relaxation in control rats but not in DM rats. These results indicate that endothelial cell dysfunction and enhanced immunoreactivity of ET-1 have been found in DM rat and ET-1-induced contraction was attenuated in DM rat. These attenuated responses might be at least in part caused by the alteration of $ET_A$ receptor properties (e.g. desensitization), and partly related with an alteration in intracellular mechanism for contraction to ET-1.

• 대한본초학회지
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• 제38권5호
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• pp.39-47
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• 2023

Objectives : The objective of present study was to investigate the vasorelaxant effects of 20 Korean native plants on isolated rat thoracic aorta precontracted with phenylephrine (PE). Methods : Dried 20 plant materials were extracted 3 times with water, ethanol, or methanol for 3h in the reflux apparatus at 70 ± 5℃. Male SD rats were anesthetized by ether inhalation, and their aorta rings were isolated and placed in 10 ㎖ Krebs Henseleit (KH) buffer. While using an isolated organ-chamber technique, the aorta rings were maintained by bubbling with a gas mixture of 95% O₂-5% CO₂ at 37℃. Changes in isometric tension of aorta rings were recorded via isometric transducers connected to a Powerlab Data Acquisition System. Results : Among the 20 native plants, Chrysanthemum indicum L. flower, Nelumbo nucifera Gaertn. rhizome, Schisandra chinensis (Turcz.) Baill. fruit, Anthriscus sylvestris (L.) Hoffm. root, Corydalis turtschaninovii Besser tuber, Corydalis decumbens (Thunb.) Pers. tuber, and Dolichos lablab L. seed showed significant vasorelaxant effect on the contraction of aorta rings induced by PE. In contrast, Mertensia maritima subsp. asiatica Takeda whole plant, Ajuga decumbens Thunb. whole plant, Trigonotis peduncularis (Trevis.) Benth. ex Baker & S.Moore whole plant, Dioscorea quinquelobate Thunb. rhizome, Allium microdictyon Prokh aerial part, Momordica charantia L. fruit, Carthamus tinctorius L. flower, and Clematis terniflora DC. root constricted more the aorta rings precontracted by PE Conclusion : These results suggest that the possibility as useful herbal resources for the development of functional foods or medicines for hypertension treatment.

• 대한약리학회지
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• 제32권1호
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• pp.51-56
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• 1996

본 연구의 목적은 2-kidney 1 clip (2K-1C) 신혈관성 고혈압흰쥐에서 심방이뇨펩이드의 혈관 이완작용의 기전을 규명하고 정상혈압흰쥐에서의 혈관이완작용과 비교하는 것이다. 2K-1C 신혈관성 고혈압흰쥐는 정상혈압흰쥐에 비하여 평균동맥압의 유의한 상승과 혈장레닌활성의 증가가 관찰되었다. 2K-1C 신혈관성 고혈압흰쥐의 대동맥에서 norepinephrine (NE)의 수축력의 감수성 및 최대 수축력이 정상혈압흰쥐의 대동맥보다 증가하였다. 심방이뇨펩타이드는 NE에 의한 수축을 농도-의존적으로 각각의 혈압군에서 억제하였다. 그러나, 2K-1C 신혈관성 고혈압흰쥐에서 심방이뇨펩타이드의 NE 억제 작용은 전체적으로 정상혈압흰쥐에서 보다 감소되었다. 그러나 최대 용량의 심방이뇨펩타이드의 NE 이완작용은 양 고혈압군에서 차이가 없었다. 2K-1C 신혈관성 고혈압흰쥐에서 NE에 의하여 $Ca^{2+}$의 유입이 유의하게 증가하였고, 심방이뇨펩타이드는 이 증가를 억제하였다. 정상혈압흰쥐에서도 심방이뇨펩타이드는 NE에 의하여 유의하게 증가된 $Ca^{2+}$의 유입을 억제하였다. 이상과 같은 결과로 볼 때 정상혈압흰쥐와 2K-1C 신혈관성 고혈압흰쥐의 심방이뇨펩타이드의 이완작용의 기전에는 $Ca^{2+}$의 유입 차단이 관여할 것으로 추측되며, 이때 심방이뇨펩타이드의 NE 수축억제에 대한 potency는 2K-1C 신혈관성 고혈압 흰쥐에서 감소하였으나 efficacy는 정상혈압흰쥐와 비교하여 변함이 없음이 관찰되었다.