• The Korea Journal of Herbology
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• v.38 no.6
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• pp.53-60
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• 2023

Objectives : The objective of present study was to investigate the vasorelaxant effects of 10 traditional Korean Herbal Prescriptions (KHP) on isolated rat thoracic aorta precontracted with potassium chloride (KCl). Methods : An electric extractor was used to extract KHP in distilled water for 3h. Rat aorta rings were isolated and were precontracted using KCl in organ chambers containing 10 ml Krebs Henseleit (KH) buffer. KHP extracts were added in increasing concentrations (10-1000 ㎍/㎖) to investigate vasorelaxant effects. The vasorelaxant responses induced by KHP were expressed as a percentage in response to contraction generated by KCl. Results : Among the 10 KHP, Gamisoyo-san, Galgeun-tang, Gyeji-tang, Gwakhyangjeonggi-san, Daeyoung-jeon, and Socheongryong-tang showed significant vasorelaxant effect at high concentration. In contrast, Gyejibokryeong-hwan constricted more the aorta rings precontracted by KCl. And Gumiganghwal-tang, Guibi-tang, Saengmaek-san showed no significant effect. Also, rat aorta rings treated with Gyejibokryeong-hwan or Gyeji-tang after pre-relaxation by amlodipine did not cause any significant change. Conclusion : Thus, these results provide the experimental evidence as useful herbal prescriptions for the treatment of hypertension and suggest guidelines in conjunction with other western drugs, including amlodipine.

• The Korean Journal of Physiology
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• v.28 no.2
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• pp.169-179
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• 1994

The effect of extracellular and intracellular pH on vascular tone and $^{45}Ca$ uptake were investigated in aortic strips and dispersed single aortic smooth muscle cells of spontaneously hypertensive rats (SHR) and aged-matched Wistar-Kyoto rats (WKY). The contraction produced by a change of extracellular pH (pHo) in the range of $6.5{\sim}8.3$ was estimated by comparison with the level of vascular tone at pH 7.4. Contraction was induced below pHo 6.5 in WKY, pHo 7.1 in SHR, and over pHo 8.0 on both strains. The amplitude of contraction induced by high pHo (over pHo 7.7) was similar in SHR and WKY, but that induced by low pHo (below pHo 7.1) in SHR was greater than that in WKY. Either high pHo- or low pHo-induced contractions in WKY and SHR were not induced in the Ca-free Tyrode's solution and were induced by the addition of Ca. $^{45}Ca$ uptake increased progressively as pHo was increased from 6.8 to 8.1 in the single aortic smooth muscle cells of WKY and SHR. $NH_4Cl$ induced a gradually developing contraction in a dose-dependent manner $(5\;mM{\sim}30\;mM)$ and the removal of $NH_4Cl$ induced transient contraction was followed by profound relaxation in the aortic rings of both strains. The contractions induced by $NH_4Cl$ or by the removal of $NH_4Cl$ in SHR were significantly greater than that in WKY. These contractions were not induced in Ca-free Tyrode's solution. $^{45}Ca$ uptake was increased by $NH_4Cl$ (20 mM) and was not changed by the removal of $NH_4Cl$ (20 mM) in the aortic strips of WKY and SHR. As a summary of above results, the vascular tone of SHR was more sensitive to the change pHi and pHo than that of WKY. The contractions induced by change of extracellular or intracellular pH depended on extracellular Ca in the aorta of SHR nnd WKY. However, the Ca uptake was in accord with the changes of contraction but increase in contraction by low pH was not accompanied by an increase in Ca uptake in both strains.

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.285-290
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• 1995

This study was undertaken to define the varying responses of vascular smooth muscle to different wavelengths of ultraviolet radiation and to relate them to the changes in cyclic GMP contents. The ring preparations of rat thoracic aorta with intact or removed endothelium were irradiated with the ultraviolet or visible light (UVR) of wavelengths in step of 10 nm between 250 and 500 nm from xenon lamp of a spectrofluorometer, and the changes in vascular tension were recorded. For cyclic GMP assay, the preparations, pretreated with phenylephrine as in the tension experinents, were frozen after irradiation and homogenated in trichloroacetic acid. The supernatant was extracted with ether and the cyclic GMP contents were measured with radioimmunoassay. In the endothelium-intact preparations, biphasic responses, vasoconstriction (UVR-contraction) followed by vasodilatation (UVR-dilatation), were observed. The maximal UVR-contraction was observed at 320 nm, while the maximal vasodilatation was elicited at 420 nm. In the endothelium-removed rings, however, only vasodilatation was observed, with the maximal vasodilatation taking place at 370 nm. The cyclic GMP contents were not affected by the Irradiation with 320 nm for 30 sec or 1 min in the endothelium-intact preparations, while it was significantly increased by 380 and 420 nm. In the endothelium-removed preparations, UVR of 370 nm markedly increased the cyclic GMP contents. The present study indicates that the increase in cyclic GMP is closely related to vasodilatation induced by UVR of 420 nm in the endothelium-intact or 370 nm in the denuded preparations, whereas it is not involved in the vasoconstriction induced by UVR of 320 nm in the intact rings, and the mechanism leading to UVR-contraction remains to be clarified. These observations suggest that nitric oxide-cyclic GMP system is closely related to the UVR-dilatation in rat aortic preparation, while it is not involved in the UVR contraction.

• Journal of Chest Surgery
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• v.28 no.8
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• pp.742-746
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• 1995

The present study was aimed at investigating possible transmitter mechanisms in the endothelial cell layer in regulating the tone of the vascular smooth muscle. The thoracic aorta was isolated from the anesthetized male white rabbits and its helical strips were prepared. Electrical field stimulation was delivered to platinum wire electrodes positioned parallel to the vessel segment preconstricted with phenylephrine [3.5x10-6 mol/L at a distance of 1.5-2.0 mm. The electrical stimulation [70 V, 5 msec, 0.5-200 Hz caused either relaxation only [34% or a biphasic response [prolonged relaxation following a weak and transient contraction, 66% . The relaxation response was frequency- dependent, and at 200 Hz a complete relaxation was noted. Mechanical rubbing of the endothelial layer abolished or greatly attenuated the relaxation. The relaxation was also markedly attenuated in the presence of NG-nitro- L-arginine methyl ester [10-3mol/L or procaine hydrochloride [3.5x10-4mol/L . Tetrodotoxin,guanethidine, atropine or indomethacin failed to block or enhance the relaxation response to electrical field stimulation. It is concluded that the vascular endothelium in the aorta contains diffusible substances that regulates the function of the smooth muscle layer, in which relaxation is more prominent than contraction. Their release by the electrical stimualtion in vitro may not involve classic neuronal transmitter release mechanisms or metabolism of arachidonic acids by cyclooxygenase. The release of the relaxing agents may require an increase in cytosolic calcium level. The chemical nature of the relaxant may be, to a large extent, nitric oxide.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.553-562
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• 2005

Melatonin, the principal hormone of the vertebral pineal gland, participates in the regulation of cardiovascular system in vitro and in vivo. Lithium inhibits both inositol polyphosphate phosphatase (IPPase) and inositol monophosphatase (IMPase), which are involved in a wide range of signal transduction pathways. The aim of the present study was to assess the effect of lithium on endothelial-dependent relaxation to melatonin and on the melatonin-induced inhibition of contraction by phenylephrine (PE) in isolated rat aorta. Melatonin induced a concentration-dependent relaxation in PE-precontracted in endothelium-intact (+E) aortic rings. Melatonin inhibited a PE-induced sustained contraction in +E aortic rings. These effects of melatonin on relaxation and contractile responses were inhibited by pretreatment with lithium. In PE-precontracted +E aortic rings, the melatonin-induced vasorelaxations and the inhibitory effects of melatonin on maximal contractions were inhibited by endothelium removal or by pretreatment with L-$N^G$-nitro-arginine (L-NNA), 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ) and nifedipine and verapamil, but not by tetrabutylammonium, clotrimazole and glibenclamide, However, in endothelium-denuded (-E) aortic rings and in the presence of L-NNA and ODQ in +E aortic rings, the melatonin-induced residual relaxations and the melatonin-induced residual contractile responses to PE were not affected by lithium. It is concluded that the inositol phosphate pathway may be involved in endothelial-dependent relaxation induced by melatonin.

• Journal of Chest Surgery
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• v.24 no.3
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• pp.229-244
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• 1991

A bioassay technique and organ bath study were performed to analyze the effects of extracellular $Ca^{2+}$ and $Ca^{2+}$-antagonists on endothelium-derived relaxing factor[s][EDRF] released from the endothelial cells of rabbit aorta. Transverse strips with intact endothelium or damaged endothelium were used for the mechanical contraction experiment using organ bath. Long segment including thoracic and abdominal aorta with endothelium [EDRF donor aorta] was perfused with Tyrode solution which was aerated with 95% $O_2-5%$ $CO_2$ mixed gas and kept at 35oC. The perfusate was bioassayed with a transverse strip of thoracic aorta with damaged endothelium. The test strip was contracted with nor-epinephrine and acetylcholine was used to stimulate the release of EDRF from endothelial cells. The results obtained were as follows; 1] The endothelium-dependent relaxation[EDR] induced by acetylcholine was biphasic; an initial rapid relaxation followed by a slow relaxation. 2] EDR induced by acetylcholine was reduced gradually with the decrease in the concentration of extracellular $Ca^{2+}$. The effect of extracellular $Ca^{2+}$ on EDR was more prominent in the late slow relaxation phase. 3] EDR to acetylcholine was not altered by acute exposure to organic $Ca^{2+}$-antagonists. Pretreatment with verapamil to the EDRF donor aortic segment did not alter the magnitude of EDR. 4] Among the inorganic $Ca^{2+}$-antagonists $Mn^{2+}$ and $Cd^{2+}$ did not inhibit EDR, whereas $Co^{2+}$ and $La^{3+}$ inhibited EDR. 5] The inhibitory response of $Co^{2+}$ to EDR developed when infused directly on the test strip. That of $La^{3+}$, however, was evoked when added to solution perfusing the donor aortic segment. The above results suggest that $Ca^{2+}$-antagonists do not affect EDR and the inhibitory effect of $Ca^{2+}$ results from influencing the action of EDRF on vascular smooth muscle, whereas that of $La^{3+}$ results from its action on the release of EDRF from endothelial cells.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.325-331
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• 2023

α₁-adrenoceptors link via the G-protein Gq/G₁₁ to both Ca²⁺ entry and release from stores, but may also activate Rho kinase, which causes calcium sensitization. This study aimed to identify the subtype(s) of α₁-adrenoceptor involved in Rho kinase-mediated responses in both rat aorta and mouse spleen, tissues in which contractions involve multiple subtypes of α₁-adrenoceptor. Tissues were contracted with cumulative concentrations of noradrenaline (NA) in 0.5 log unit increments, before and in the presence of an antagonist or vehicle. Contractions produced by NA in rat aorta are entirely α₁-adrenoceptor mediated as they are competitively blocked by prazosin. The α_1A-adrenoceptor antagonist RS100329 had low potency in rat aorta. The α_1D-adrenoceptor antagonist BMY7378 antagonized contractions in rat aorta in a biphasic manner: low concentrations blocking α_1D-adrenoceptors and high concentrations blocking α_1B-adrenoceptors. The Rho kinase inhibitor fasudil (10 µM) significantly reduced aortic contractions in terms of maximum response, suggesting inhibition of α_1B-adrenoceptor mediated responses. In the mouse spleen, a tissue in which all 3 subtypes of α₁-adrenoceptor are involved in contractions to NA, fasudil (3 µM) significantly reduced both early and late components to the NA contraction, the early component involving α_1B- and α_1D-adrenoceptors, and the late component involving α_1B- and α_1A-adrenoceptors. This suggests that fasudil inhibits α_1B-adrenoceptor mediated responses. It is concluded that α_1D- and α_1B-adrenoceptors interact in rat aorta and α_1D-, α_1A- and α_1B-adrenoceptors interact in the mouse spleen to produce contractions and these interactions suggest that one of the receptors preferentially activates Rho kinase, most likely the α_1B-adrenoceptor.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.21-31
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• 1996

To investigate the mechanisms of increased endothelium-dependent contraction by acetylcholine in hypertensive rats, the relationship between endothelium-dependent contraction by acetylcholine and blood pressure was studied in spontaneously hypertensive rats (SHR), one-kidney, one clip Goldblatt hypertension (1K,1C-GBH) rats, and Wistar-Kyoto rats (WKY). SHR were treated orally with enalapril or nicardipine in order to prevent development of hypertension or suppress the developed hypertension. 1K,1C-GBH rats were made by renal artery stenosis with contralateral nephrectomy in 8 week-WKY. 1. Endothelium-dependent contractions by acetylcholine $(10^{-6}{\sim}10^{-5}\;M)$ in SHR were significantly greater than those in WKY. 2. Chronic treatment with enalapril or nicardipine reduced the endothelium-dependent contraction in SHR 3. The degree of reduction of endothelium-dependent contraction was greater in SHR which was prevented from developing hypertension than in SHR of which high blood pressure was suppressed. 4. In aortic rings from 1K,1C-GBH rats, endothelium-dependent contractions by acetylcholine were augmented as compared with WKY. 5. There is good relationship between the value of blood pressure and magnitude of endothelium-dependent contraction. Thus, it is suggested that increased endothelium-dependent contraction in hypertensive rats may he due to the high blood pressure and endothelium-dependent contraction may not be a cause of the initiation of hypertension in SHR.

• The Korean Journal of Physiology
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• v.23 no.1
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• pp.99-108
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• 1989

The effects of prostaglandin $(PGF_{2{\alpha}})$ on the contractility of vascular smooth muscle were investigated in the helical strip of the rabbit aorta. The aortic strip was immersed in the phosphate-buffered Tyrode's solution which was equilibrated with 100% $O_{2}$ at $35^{\circ}C$ and its isometric tension was measured. The contraction was induced by $(PGF_{2{\alpha}})$, norepinephrine (NE), or potassium (40 mM) in the nomal Tyrode's solution (1 mM, $Ca^{2+}$) or $Ca^{2+}-free$ Tyrode's solution. Effects of verapamil and phentolamine on the contraction were also observed. The aortic strip began to contract at the concentration of $5\;{\mu}g%$ and reached the maximal contraction at the concentration of $150\;{\mu}g%$ $(PGF_{2{\alpha}})$. The maximal contraction was corresponded respectively to $52.2{\pm}3.0%$ and $81.5{\pm}3.5%$ of maximal contraction by NE $(1{\times}10^{-5}M)$ and 40 mM $K^{+}$. And the maximal contractions by $(PGF_{2{\alpha}})$ or NE were induced at the concentration of about 1 mM $Ca^{2+}$. $(PGF_{2{\alpha}})$ induced the contraction of aortic strip even after induction of contraction by 40 mM $K^{+}$ and the contraction by $(PGF_{2{\alpha}})$ was not blocked by the ${\alpha}-receptor$ blocker, phentolamine. And the contraction by the $(PGF_{2{\alpha}})$ was inhibited partially by a verapamil at the concentration of $1{\times}10^{-5}M$ and the contraction began to increase at the concentration of $1{\times}10^{-4}M$ verapamil. Whereas the contraction by NE was completely blocked by verapamil. Though both the $(PGF_{2{\alpha}})$ and NE induced the contraction in the $Ca^{2+}-free$ Tyrode's solution, the peak tension was not maintained. But the rate of tension decline was lower in the contraction by $(PGF_{2{\alpha}})$ than in that by NE. The verapamil did not inhibit the contraction by $(PGF_{2{\alpha}})$ in the $Ca^{2+}-free$ Tyrode's solution and increased the contraction at the concentration of above $1{\times}10^{-4}M$. The NE-induced contraction in the $Ca^{2+}-free$ Tyrode's solution was inhibited completely by a verapamil. From the above results it is suggested that the contraction induced by $(PGF_{2{\alpha}})$ results from the promotion of the both $Ca^{2+}$ influx and the intracellular $Ca^{2+}$ release by different way from NE.

• Herbal Formula Science
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• v.11 no.2
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• pp.125-134
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• 2003

We have examined the relaxational response to the water extract of Angelica gigas $N_{AKAI}$ (AG), Gingko biloba $L_{INNE}$ (GB), Acanthopanax senticosus $H_{ARMS}.$ (AP) and Augumented-Four-Substance Decoction (AG-FSD, GB-FSD, AP-FSD) in 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 AG, GB, AP and AG-FSD, GB-FSD, AP-FSD were investigated in vessels precontracted with 5-hydroxytryptamine(5-HT) were compared in vasodilation effect. We found that the thoracic aorta segments responded to AG, GB, AP and AG-FSD, GB-FSD, AP-FSD with a dose-dependent vasodilation. The 5-hydroxytryptamine induced contraction at $10^{-4}M$ were inhibited by 26.3%, 75.8%, 87.5% and 6.9%, 22.6%, 30.8% after addition of the 0.1 g/mL water extract of AG, GB, AP and AG-FSD, GB-FSD, AP-FSD. In conclusion, AG, GB, AP and AG-FSD, GB-FSD, AP-FSD induced relaxation in the isolated rat thoracic aorta were composed of dose-dependent relaxation. AP-FSD has very potent vasodilation.