• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.255-262
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• 2022

Oxytocin is a neuropeptide produced primarily in the hypothalamus and plays an important role in the regulation of mammalian birth and lactation. It has been shown that oxytocin has important cardiovascular protective effects. Here we investigated the effects of oxytocin on vascular reactivity and underlying the mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and in rat aorta ex vivo. Oxytocin increased phospho-eNOS (Ser 1177) and phospho-Akt (Ser 473) expression in HUVECs in vitro and the aorta of rat ex vivo. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited oxytocin-induced Akt and eNOS phosphorylation. In the rat aortic rings, oxytocin induced a biphasic vascular reactivity: oxytocin at low dose (10^-9-10^-8 M) initiated a vasorelaxation followed by a vasoconstriction at high dose (10^-7 M). L-NAME (a nitric oxide synthase inhibitor), endothelium removal or wortmannin abolished oxytocin-induced vasorelaxation, and slightly enhanced oxytocin-induced vasoconstriction. Atosiban, an oxytocin/vasopressin 1a receptor inhibitor, totally blocked oxytocin-induced relaxation and vasoconstriction. PD98059 (ERK1/2 inhibitor) partially inhibited oxytocin-induced vasoconstriction. Oxytocin also increased aortic phospho-ERK1/2 expression, which was reduced by either atosiban or PD98059, suggesting that oxytocin-induced vasoconstriction was partially mediated by oxytocin/V1aR activation of ERK1/2. The present study demonstrates that oxytocin can activate different signaling pathways to cause vasorelaxation or vasoconstriction. Oxytocin stimulation of PI3K/eNOS-derived nitric oxide may participate in maintenance of cardiovascular homeostasis, and different vascular reactivities to low or high dose of oxytocin suggest that oxytocin may have different regulatory effects on vascular tone under physiological or pathophysiological conditions.

• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.19-24
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• 2004

The vascular relaxant effect of amlodipine adipate, a new salt of amlodipine, was evaluate in isolated rat aorta, and compared with that of amlodipine besylate. Furthermore, antihypertensive effects were measured in hypertensive rat models, such as spontaneously hypertensive rats (SHR) and rena1 hypertensive rats (RHR). Amlodipine adipate concentration-dependently inhibited $Ca^{2+}$-induced contraction of rat aorta with a very slow onset of action (reached its maximum at 3.5 h;$IC_{50}$: 3.76 nM), having a pattern and a potency similar to those of amlodipine besylate ($IC_{50}$: 4.01 nM). In SHR and RHR, orally administered amlodipine adipate produced a dosedependent and long-lasting (>10-24 h) antihypertensive effect ($ED_{20}$: 2.48 and 1.57 mg/kg, respectively), with a pattern and a potency similar to those of amlodipine besylate ($ED_{20}$: 2.50 and 1.99 mg/kg in SHR and RHR, respectively). These results suggest that amlodipine adipate is a potent and long-lasting antihypertensive agent and that its antihypertensive effect is not significantly different to that of amlodipine besylate.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.390-401
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• 1997

In order to investigate the pharmacological properties of New Woohwangchungsimwon Liquid (NCL), effects of Woohwangchungsimwon Liquid (CL) and NCL were compared. In isolated rat aorta, NCL and CL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) without regard to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxation of NCL and CL. NCL and CL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NCL and CL significantly decreased heart rate. NCL and CL, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NCL and CL had no effects on parameters of action potential at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NCL and CL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between two preparations.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.66-78
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• 1999

In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD$_{90}$ and V$_{max}$ at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.s.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1078-1082
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• 2004

The purpose of this study was to investigate the possibility of medicinal plants application as an edible functional food resources. We carried out to develop a traditional functional beverage by using hot-water extraction of 4 medicinal plants(Polygonatun sibiricum, Ophiopogonis radix, Lycii fructus, Schizandriae fructus) and we examined the effects of drink on physiological function in aorta relaxation. Thus, the effect of developed beverage on phenylephrine induced contraction of isolated rat thoracic aorta. Contractile force was measured with force displacement transducer under 1.5g loading tension. Brix, pH and titratable acidity of developed drink were 9.5%, 3.3 and 0.22%. The approximate nutritional composition of beverage was carbohydrate, 5.98%, crude protein, 0.70%, crude fat, 0.20% and crude ash, 0.20%. Developed beverage contained K(4.00 ㎎%), Na(3.68 ㎎%), Ca(2.54 ㎎%), Mg(1.60 ㎎%) and Fe(0.29㎎%). The contraction forces by injection of phenylephrine in isolated thoracic aorta were significantly low in each experimental groups compared with control groups, These results that developed drink with medicinal plants can be used as a functional material to decrease aorta contraction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.2
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• pp.490-494
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• 2005

The purpose of this was investigate the possibility of medicinal plants application as an edible functional food resources. We arried out to develop a beverage by using Nelumbo nucifera and we examined the nutritional characterics. Also we examined the effects of drink on physiological function in aorta relation. Thus, the effect of developed beverage on phenylephrine induced contraction of isolated rat thoracic aorta. Contractile force was measured with force displacement thansducer under 1.5g loading tension. Brix, pH and titratable acidity of developed drink were 12.25%, 4.5 and 0.092%. The approximate nutritional composition of beverage was carbohydrate, 9.40%, crude protein, 0.30%, crude fat, 0.25% and ash, 0.15%. Also insoluble fiber and soluble fiber were 1.30%, 0.80%. Developed beverage contained Na(11.45 mg%), K(6.87 mg%), Ca(2.53 mg%). The contraction forces by injection of phenylephrine in isolated thoracic aorta were significantly law in each beverage treatment groups compared with control group. These results that developed drink with medicinal plants can be used as a functional material to decrease aorta contraction.

• The Korea Journal of Herbology
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• v.38 no.5
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.217-223
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• 1998

Oxygen-derived free radicals have been implicated in many important functions in the biological system. Electrical field stimulation (EFS) causes arterial relaxation in animal models. We found that EFS applied to neither muscle nor nerve but to Krebs solution caused a relaxation of rat aorta that had been contracted with phenylephrine. In the present study, therefore, we investigated the characteristics of this EIRF (electrolysis-induced relaxing factor) using rat isolated aorta. Results indicated that EIRF acts irrespective of the presence of endothelium. EIRF shows positive Griess reaction and is diffusible and quite stable. EIRF-induced relaxation was stronger on PE-contracted aorta than on KCl-contracted one, and inhibited by the pretreatment with methylene blue. Zaprinast, a cGMP-specific phosphodiesterase inhibitor, potentiated the EIRF-induced relaxation. $N^G-nitro-L-arginine$, NO synthase inhibitor, did not inhibit the EIRF-induced relaxation. Deferroxamine, but not ascorbic acid, DMSO potentiated the EIRF-induced relaxation. These results indicate that electrolysis of Krebs solution produces a factor that relaxes vascular smooth muscle via cGMP-mediated mechanism.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1036-1040
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• 2004

The purpose of the present study is to measure the effect of Tuber Pinelliae on EP(epinephrine) induced contraction of isolated rat thoracic aorta. Contractile force was measured with force displacement transducer under 1.5g loading tension. The mean percent increasing of rCBF was 11.4% (p<0.05) after 10㎎/㎏ Tuber Pinelliae. Contractions evoked by EP (ED50) and KCI 65.4mM were decreased significantly by Tuber Pinelliae. L-NNA, ODQ and atropine significantly altered the effect of Tuber Pinelliae, but propranolol and indomethacin did not change the relaxation of Tuber Pinelliae. These results indicate that Tuber Pinelliae can relax EP and KCI induced contraction of isolated rat thoracic aorta and that this decreasing contraction related to epithelium, nitric oxide, and parasympathetics.

• Biomolecules & Therapeutics
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• v.11 no.2
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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.