• Advances in Traditional Medicine
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• v.7 no.3
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• pp.261-273
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• 2007

We investigated the antihypertensive effect of Pet ether extract (PE) of ginger rhizome; its toluene fraction (TF) and Korean ginseng extract (KGE) in deoxycorticosterone acetate (DOCA) - salt induced and fructose induced hypertensive rats. In DOCA model, DOCA (25 mg/kg, once a week; s.c) was administered in uninephrectomised animals for 4 w. PE (50 mg/kg/day; p.o), TF (10 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) were evaluated for their antihypertensive effect. In the fructose model, drinking water was replaced with fructose (10%) for five weeks to induce hypertension. PE (50 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) were assessed for its antihypertensive effect in fructose model. After completion of the treatment schedule, vascular reactivity to various agonists like 5-HT, noradrenaline, adrenaline, phenylbiguanide and acetylcholine were recorded in rats of both the models. A cumulative dose response curve (CDRC) of 5-HT was carried out in isolated rat fundus strip of the fructose induced hypertensive rats. Chronic administration of PE (50 mg/kg/day; p.o), TF (10 mg/kg/day; p.o), and KGE (30 mg/kg/day; p.o) significantly reduced the blood pressure in DOCA salt whereas PE (50 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) reduced the blood pressure in fructose induced hypertensive rats. Treatment with PE (50 mg/kg/day; p.o) and KGE (30 mg/kg/day; p.o) in fructose model for five weeks shifted the CDRC towards the right on rat fundus. The mechanism of action may partly involve the serotonergic antagonistic property.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.1
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• pp.162-170
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• 2008

Kamisungihwalhyul-tang(KSHT) has been used for many years as a therapeutic agent for cerebrovascular disease and hypertension in Oriental Medicine. But the effect of KSHT on hypertension and reactive oxygen is not well-known. This study was examined to investigate the effect of KSHT on hypertension and reactive oxygen. After administering KSHT extract to Sprague- Dawley Rat forinjected subcutaneous with deoxycorticosterone acetate(DOCA) 8 weeks, changes in blood pressure, pulse rate, 2,2-diphenyl-1-picrylhydrazyl, reactive oxygen species, angiotensin converting enzyme, aldosterone, catecholamine levels, electrolyte, uric acid, BUN, creatinine in plasma were examined, and immunohistochemical changes and scanning electron microscopic changes were observed. 2,2-diphenyl-1-picrylhydrazyl(DPPH) scavenging activity was increased, reactive oxygen species(ROS) was decreased in a KSHT concentration-dependent. Angiotensin converting enzyme(ACE) inhibitory activity was increased in a concentration-dependent by KSHT. KSHT significantly decreased the blood pressure and heart rate in DOCA-salt hypertensive rat. KSHT significantly decreased the levels of aldosterone in DOCA-salt hypertensive rat. KSHT significantly decreased the level of dopamine, norepinephrine, epinephrine in DOCA-salt hypertensive rat. $Na^+$, $K^+$ and Cl- were decreased significantly, $Ca^{2+}$ was increased significantly by KSHT. KSHT significantly decreased uric acid, BUN, creatinine.

• Journal of Korean Physical Therapy Science
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• v.10 no.1
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• pp.158-169
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• 2003

The present study examined that in vivo test is investigated in sham-operated(control group) and aldosterone-analogue deoxycorticosterone acetate (DOCA)-salt hypertensive animals(experimental group) and that the antihypertensive effect was induced by silver spike point(SSP) low frequency electrical stimulation at meridian points(CV-3, -4, Ki-12, SP-6, LR-3, BL-25, -28, -32, -52), specifically, such as diuretic action in 24 hour urine analysis from normal volunteer. The $Na^+$ and $Ca^{2+}$ ions were significantly increased in aldosterone-analogue DOCA-salt hypertensive rats than that in sham-operated rats. However, the $K^+$ ions were significantly decreased in aldosterone-analogue DOCA-salt hypertensive rats than that in sham-operated rats. The current of 1 Hz continue type of SSP low frequency electrical stimulation significantly increased in excretion of urine $Na^+$ and $K^+$ ions from normal volunteer. However, the excretion of $Ca^{2+}$ ion were significantly decreased by SSP electrical stimulation in volunteer. These results suggest that the development of aldosterone analogue-DOCA-salt hypertension is associated with changed $Na^+$, $K^+$ and $Ca^{2+}$ ions of urine. which directly affects blood pressure. Therefore, the hypertension is a risk factor on cardiovascular disease. Moreover, These results demonstrate that the SSP low frequency electrical stimulation, especially current of 1 Hz continue type, significantly regulates $Na^+$, $Ca^{2+}$ and $K^+$ ions from volunteer. Therefore, the SSP low frequency electrical stimulation is a good regulator through a diuretic action of aldosterone-induced hypertension.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.5
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• pp.529-535
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• 1997

The present study was aimed at investigating whether the vascular calcium regulation is altered in hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in rats, and their thoracic aortae were taken 4 weeks later. The isometric contractile response and calcium uptake of the endothelium-denuded aortic preparations were determined. Caffeine ($0.1{\sim}35\;mmol/L$) induced a greater contraction in 2K1C and DOCA-salt hypertension than in normotensive control. When the vascular calcium store was functionally-depleted by a repeated exposure to caffeine, it took longer to reload the store and to resume the initial contraction force in response to caffeine in both 2K1C and DOCA-salt hypertension. The vascular $^{45}Ca$ uptake following the functional depletion of the cellular store was also greater in both models of hypertension than in control. Ryanodine, calcium channel activator of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced vascular contraction, which was not affected by either 2K1C or DOCA-salt hypertension. Nifedipine, an L-type $Ca^{2+}$ channel blocker, attenuated the restoration of caffeine-induced contraction, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Nifedipine also diminished the vascular $^{45}Ca$ uptake, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Ouabain, a $Na^+,\;K^+-ATPase$ inhibitor, increased the caffeine-induced contraction by a similar magnitude in control and 2K1C hypertension, which was, however, markedly attenuated in DOCA-salt hypertension. Ouabain enhanced the vascular $^{45}Ca$ uptake, the degree of which was not affected by 2K1C hypertension, but was markedly attenuated in DOCA-salt hypertension compared with that in control. Cyclopiazonic acid, a selective inhibitor of $Ca^{2+}-ATPase$ of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced contraction, which was not affected by 2K1C hypertension, but was more marked in DOCA-salt hypertension. These results suggest that the increased vascular calcium storage may be attributed to an enhanced calcium influx in 2K1C hypertension, and to an impaired $Na^+-K^+$ pump activity of the cell membrane and subsequently increased calcium pump activity of the cellular store in DOCA-salt hypertension.

• Journal of Korean Physical Therapy Science
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• v.13 no.2
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• pp.67-83
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• 2006

The present study examined that in Vivo/Vitro test is investigated in normotensive sham-operated rats (NSR) and aldosterone-analogue deoxycorticosterone acetate (DOCA)-salt hypertensive rats (ADHR) and that the antihypertensive effect was induced by silver spike point (SSP) electrical stimulation at meridian points(CV-3, -4, Ki-12, SP-6, LR-3, BL-25, -28, -32, -52), specifically, such as aldosterone in 24 hour urine analysis from healthy volunteer. The gross examination and morphometric-histological changes, such as hypertrophy, production of necrotic tissues, and the changes of cell arrangement on the kidney, and adrenal gland were markedly observed in aldosterone-analogue DOCA-salt hypertensive rats compared with those from normotensive sham-operated rats. The systolic blood pressure, weight of kidney and adrenal gland were significantly increased in ADHR than that in NSR. The required time of PSS-induced resting tone was significantly increased in ADHR than that in NSR. However, the voltage-dependent K+ (Kv) currents were significantly decreased in ADHR than that in NSR. The urine analysis showed that the concentration of aldosterone was significantly decreased in resting state from the elderly people compared with those from the adolescent healthy volunteer. The current of 1 Hz continue type of SSP electrical stimulation significantly decreased in the concentration of aldosterone of 24 hour urine from the elderly people. These results suggest that the development of aldosterone analogue-induced hypertension is associated with changed the weight of kidney and adrenal gland, blood pressure, resting tone and Kv currents, which directly affects blood pressure. Therefore, the hypertension is a risk factor on cerebrovascular disease. Moreover, these results suggest that the diminished responsiveness to SSP electrical stimulation, especially current of 1Hz continue type, in elderly people may be, in part, related by the increased of antihypertensive effects.

• Journal of Korean Physical Therapy Science
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• v.13 no.2
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• pp.137-145
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• 2006

We investigated whether increased contractile responsiveness to epidermal growth factor (EGF) is associated with altered activation of mitogen-activated protein kinase (MAPK) in the aortic smooth muscle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. EGF induced contraction and MAPK activity in aortic smooth muscle strips, which were significantly increased in tissues from the DOCA-salt hypertensive rats compared with those from sham-operated rats. AG1478, PD98059, and LY294002, inhibitors of EGF receptor (EGFR) tyrosine kinase, MAPK/extracellular signal-regulated kinase (ERK) kinase, and phosphatidylinositol 3-kinase (PI3K), respectively, inhibited the contraction and the activity of ERK1/2 that were elevated by EGF. Y27632 and GF109203X, inhibitors of Rho kinase and protein kinase C, respectively, attenuated EGF-induced contraction, with no diminution of ERK1/2 activity. Although EGF also elevated the activity of EGFR tyrosine kinase in both sham-operated and DOCA-salt hypertensive rats, the expression and the magnitude of activation did not differ between strips. These results strongly suggest that EGF induces contraction by the activation of ERK1/2, which is regulated by the PI3K pathway in the aortic smooth muscle of DOCA-salt hypertensive rats.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.1024-1031
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• 2006

The role of mitogen-activated protein kinase (MAPK) in the decreased contractile response to phorbol ester in aortic smooth muscle strips from deoxycorticosterone acetate (DOCA)-salt hypertensive rats was examined. Norepinephrine (NE) evoked greater contractility in aortic strips from DOCA rats than in those of sham-operated rats. 12-Deoxyphorbol 13-isobutyrate (DPB) induced contraction in $Ca^{2+}-free$ medium, which was diminished in strips from DOCA rats compared to sham-operated rats. Vasoconstrictions induced by these stimulants were inhibited by SB203580 and PD098059, inhibitors of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2, respectively, in both strips. The phosphorylation of p38 MAPK and ERK1/2 induced by NE was greater in strips from DOCA rats compared to those from sham-operated rats, and this phosphorylation was inhibited by the kinase inhibitors. DPB increased the phosphorylation of p38 MAPK and ERK1/2 in strips from both animals, and the increment of p38 MAPK phosphorylation by the stimulant was diminished in strips from DOCA rats compared to sham-operated rats. These findings suggest that the $Ca^{2+}-independent$ contraction evoked by DPB results from the activation of MAPKs in rat aortic smooth muscle and that the attenuated contractility by DPB in DOCA rat appears to be associated with diminished p38 MAPK activity.