• Archives of Pharmacal Research
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• v.19 no.6
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• pp.456-461
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• 1996

Vascular relaxation action of crude extracts of two kinds of Coptidis rhizoma (Coptis chinensis and Coptis japonica, Ranunculaceae) was investigated and compared with that of berberine and palmatine, active alkaloid components of these plants. The results show that total extracts, berberine, and palmatine induced a concentration-dependent vasodilatation of rat thoracic aorta contracted with phenylephrine (PE). Palmatine, unlike to berberine, did not inhibit contraction induced by KCI. In calcium-free media, not only berberine but also crude extracts inhibited calcium-induced contraction. Furthermore, pretreatment of crude extracts inhibited contraction induced by PE noncompetitively. In PE-induced contraction, berberine was 2.5 times more potent than Coptis chinensis in the relaxation of rat aorta in terms of $IC_{50}$ values. Analysis of the effects of crude extracts on the Emax and $IC_{50}(PE)IC_{50}(KCI)$ ratios provides information on selectivity and indicates that extracts exhibit greater inhibition of the contrac tile response induced by PE than by KCI. We concluded that crude extracts have .alpha.-adrenoceptor blocking action and possesses inhibitory effect on calcium influx, which may be at least in part responsible for the antihypertensive action.

• YAKHAK HOEJI
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• v.44 no.1
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• pp.80-86
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• 2000

TEA, glibenclamide, L-NAME and SKF 525A-induced contraction were investigated using acetylcholine, sodium nitroprusside (SNP, NO donor) and pinacidil (ATP sensitive $K^{+}$ channel opener) in rat abdominal and thoracic aorta. The relaxant effects of acetylcholine, SNP and pinacidil were not different in the abdominal aorta and in the thoracic aorta. Acetylcholine-induced relaxation was dependent on endothelial cell, but pinacidil was independent endothelia cell. In the presence of TEA, glibenclamide, L-NAME, mepacrine and SKF 525A, acetylcholine and SNP did not change, but pinacidil-induced relaxation was significantly reduced in presence of glibenclamide, which is ATP sensitive $K^{+}$ channel blocker. SKF 525A, which is inhibitor of cytochrome P$_{450}$ dependent epoxygenase, partially inhibited the pinacidil-induced relaxation. These results indicate that the pinacidil-induced relaxation may be mediated by ATP sensitive $K^{+}$ channel and partially by EETs, which is produced by cytochrome P$_{450}$ dependent epoxygenase.enase.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.299-305
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• 1997

In order to investigate the pharmacological properties of ι-muscone, effects of ι-muscone and musk were studied on the cardiovascular system with various experimental models. In isolated rat aorta, ι-muscone and musk made the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) in endothelium-containing rings of the rat aorta, but not in endothelium-denuded rings. However, ι-muscone and musk in the presence of the inhibitor of NO synthase and guanylate cyclase did not make the relaxation of blood vessels. In spontaneously hypertensive rats (SHRs), ι-muscone and musk slightly reduced blood pressure but significantly decreased heart rate. In the isolated perfused rat hearts, ι-muscone and musk did not affect significantly on LVDP, contractile force, coronary flow and (-dp/dt)/(+dp/dt). These results suggest that ι-muscone and musk have weak cardiovascular effects with relaxation of blood vessel and decrease of heart rate, but without significant cardiac functions.

• Journal of Ginseng Research
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• v.7 no.1
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• pp.1-12
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• 1983

This study was divised to observe the effects of ginseng on the body components of Sprague-Dowley Albino male rats by alternating the diet. Just weaned rats (130 heads, weighing(83 ${\pm}$ 4g) were fed with each stock diets supplemented with 0.5, 1.0 or 3.0% ginseng powder for 4 weeks or 8 weeks, and after that fed with stock diet only for 8 or 4 weeks. Compared with the each corresponding group which was fed with ginseng control diet, the protein, total lipid, total cholesterol and free cholesterol contains in serum, liver and aorta of them were determined. The results obtained was summarized as follows ; Protein and total lipid contents of the rat were decreased, caused by the alternating diets, but total cholesterol and free cholesterol contents were increased in the serum, protein and free cholesterol contents increased, conversely total lipid contents decreased in the liver, and in aorta total lipid and total cholesterol contents decreased, In the view of the above results, it can be seen that the alternating diet (stock diet after feeding with ginseng diet) has an influence on the body components of rat.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.461-469
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethy-lamines, and many of them, especially with 6,7-disubstitution, demonstrate relatively high affinity for catecholamines. Two -OH groups at 6 and 7 positions are supposed to be essential to exert ?${\beta}-receptor$ activities. However, it is not clear whether -OH at 6,7 substitution of THIs also shows ?${\alpha}-adrenoceptor$ activities. In the present study, we investigated whether -OH or $-OCH_3$ substitutions of 6,7 position of THIs differently affect the ?1-adrenoceptor affinity. We synthesized two 1-naphthylmethyl THI alkaloids, $1-{\beta}-naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline$ HBr (YS 51) and $1-{\beta}-naphthylmethyl-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline$ HCl (YS 55), and their pharmacological actions on ?${\alpha}_1-adrenoceptor$ were compared. YS 51 and YS 55, concentration-dependently relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.89{\pm}0.21$ and $5.93{\pm}0.19$, respectively. Propranolol (30 nM) did not affect the relaxation-response curves to YS 51 and YS 55. Concentration-response curves to PE were shifted to right by the pretreatment with YS 51 or YS 55. The $pA_2$ values of YS 51 and YS 55 showed $6.05{\pm}0.24$ and $5.88{\pm}0.16$, respectively. Both probes relaxed KCl (65.4 mM)-contracted aorta and inhibited $CaCl_2-induced$ contraction of PE-stimulated endothelium- denuded rat thoracic aorta in $Ca^{2+}-free$ solutions. In isolated guinea pig papillary muscle, 1 and 10 ${\mu}M$ YS 51 increased contractile force about 4- and 8- fold over the control, respectively, along with the concentration-dependent increment of cytosolic $Ca^{2+}$ ions. While, 10 ${\mu}M$ YS 55 reduced the contractile force about 50 % over the control and lowered the cytosolic $Ca^{2+}$ level, in rat brain homogenates, YS 51 and YS 55 displaced $[^3H]prazosin$ binding competitively with Ki 0.15 and 0.12 ${\mu}M$, respectively. However, both probes were ineffective on $[^3H]nitrendipine$ binding. Therefore, it is concluded that two synthetic naphthylmethyl-THI alkaloids have considerable affinity to ?1-adrenenoceptors in rat aorta and brain.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.323-330
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats' isolated atria and aorta. In addition, a $[^3H]$ prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have ?${\alpha}$-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.56{\pm}0.32$ and $5.55{\pm}0.21$, $5.99{\pm}1.16$ and $5.57{\pm}0.34$, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right and resulted in $pA_2$ values of $8.07{\pm}0.84$ and $7.93{\pm}0.11$, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac ?${\beta}-adrenoceptors$. YS 49, YS 51, and higenamine showed ?${\alpha)-adrenoceptor$ affinity in rat brain, in which the dissociation constant $(K_i)$ was 2.75, 2.81, and 1.02 ${\mu}M$, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to ${\alpha)_1-adrenoceptor$ in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac ${\beta}-adrenoceptors$. Thus, these chemicals may be useful in the treatment of congestive heart failure.

• The Journal of the Korean dental association
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• v.19 no.7 s.146
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• pp.609-614
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• 1981

Effects of steroid hormones on the collagen biosynthesis in aorta and uterus were studied with ovariectomized Sprague-Dawley rats. Effects of administration of hormones, such as estrogen, testosterone and prednisolone, to the ovariectomized animals were studied, comparing with the control. Each group was injected with ³H-proline and sacrificed, followed by removals of aorta and uterus. Separations and quantitative analyses of proline and hydroxyproline were performed by means of thin layer chromatography; and radioactivities of the separated amino acids were assayed by liquid scintillation counter. Normally the incorporation of ³H-proline into hydroxyproline was greater in uterus than in aorta, and collagen turnover rate of uterus was observed rapid as well than that of aorta. In the two tissues from ovariectomized rats, the incorporation rate of ³H-proline into hydroxypoline was markedly decreased than that of the former. Changes in the turnover rate of collagen in these tissues were not observed. Decrease in ³H-proline incorporation into collagen in ovariectomized rats was markedly antagonized by estrogen, but not influenced by prednisolone in the tissues tested.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.597-606
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• 2003

Although the antidepressant effects of imipramine (IMI) have been well known in several studies, the effects on cardiovascular system, particularly the vasorelaxant effects, have not known clearly. We hypothesis that IMI-induced vasorelaxation involves NO (nitrie oxide), activation of guanylate cyclase (GC) and $Ca^{2+}$ channel. The possible roles of the endothelium and $Ca^{2+}$ in IMI-induced responses were investigated using isolated rings of rat thoracic aorta and anesthesized rats. In KCl-precontracted rings. IMI produces endothelium-dependent and endothelium-independent relaxations in intact (+E) as well as endothelium-denuded (-E) rat aorta in a concentration-dependent manner. In phenylephrine (PE)-precontracted rings, the IMI-induced relaxation was significantly greater in +E rings. The IMI-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, a non-selective GC inhibitor, methylene blue, $Na^+$ channel blockers, lidocaine and procaine, or $Ca^{2+}$ channel blockers, nifedipine and verapamil, in PE-precontracted +E rings, but not in PE-precontracted -E rings. These relaxations were also suppressed by lidocaine or procaine in -E aortic rings. However, IMI-induced relaxations were not inhibited by a PLC inhibitor 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC), an inositol monophosphatase inhibitor, lithium, indomethacin and dexamethasone in +E and -E rings. In vivo, infusion of IMI elicited significant decrease in arterial blood pressure. After intravenous injection of saponin, NOS inhibitors. MB and nifedipine, infusion of IMI inhibited the IMI-lowered blood pressure markedly. These findings suggest that the endothelium-dependent relaxation induced by IMI is mediated by activation of NO/cGMP signaling cascade or inhibition of $Ca^{2+}$ entry through voltage-gated channel, and this mechanism may contribute to the hypotensive effects of IMI in rats.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.629-638
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• 2006

This study was carried out to examine the relaxational response to the water extract of Sobokchuko-tang (SCT) in rat thoracic aorta. Segments of thoracic aorta obtained from rats immediately after delivery were mounted in organ baths superfused on a polygraph. It was found that the thoracic aorta segments responded to the SCT with dose-dependent vasorelaxation. At $10^{-7}M$ phenylephrine-induced contraction, the contractile response of thoracic aortic rings were inhibited by 99.2%. 75.3%. 42.4% and 35.8% after addition of the respective concentration (1O. 30. 100. $300{\mu}g$/ml) of SCT. This vasorelaxation of rat thoracic aorta was endothelium-dependent. The action mechanisms of vasorelaxation are thought to be concerned with the role of NO. cAMP and cyclooxygenase. but not with cGMP.

• Journal of Nutrition and Health
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• v.53 no.6
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• pp.563-569
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• 2020

Purpose: The vascular smooth muscle cells (VSMCs) in mature animals have implicated to play a major role in the progression of cardiovascular diseases such as atherosclerosis. This study aimed at optimizing the protocol in culturing primary VSMCs (pVSMCs) from rat thoracic aorta and investigating the effect of cellular zinc (Zn) deficiency on cell proliferation of the isolated pVSMCs. Methods: The thoracic aorta from 7-month-old Sprague Dawley rats was isolated, minced and digested by the enzymatic process of collagenase I and elastase, and then inoculated with the culture Dulbecco Modified Eagle Medium (DMEM) at 37℃ in an incubator. The primary cell culture morphology was observed using phase-contrast microscopy and cellular Zn was depleted using Chelex-100 resin (extracellular zinc depletion only) or 3 µM N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) (extracellular and intracellular zinc depletion). Western blot analysis was used for the detection of SM22α and calponin as smooth muscle cell marker proteins and von Willebrand factor as endothelial cell marker protein to detect the culture purity. Cell proliferation by Zn depletion (1 day) was measured by MTT assay. Results: A primary culture protocol for pVSMCs from rat thoracic aorta was developed and optimized. Isolated cultures exhibited hill and valley morphology as the major characteristics of pVSMCs and expressed the smooth muscle cell protein markers, SM22α and calponin, while the endothelial marker von Willebrand factor was hardly detected. Zn deprivation for 1 day culture decreased rat primary vascular smooth muscle cell proliferation and this pattern was more prominent under severe Zn depletion (3 µM TPEN), while less prominent under mild Zn depletion (Chelexing). Conclusion: Our results suggest that cellular Zn deprivation decreased pVSMC proliferation and this may be involved in phenotypic modulation of pVSMC in the aorta.