• 대한물리치료과학회지
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• 제10권1호
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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.

• Advances in Traditional Medicine
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• 제7권3호
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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.

• The Journal of Korean Physical Therapy
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• 제20권4호
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• pp.35-42
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• 2008

Purpose: Alterations in the structure and function of vascular smooth muscle cells (VSMCs) are important in cardiovascular disease and maintaining chronic hypertension. Chronic hypertension is associated with changes in vascular smooth muscle tone. The spontaneous or myogenic tone of a blood vessel reflects the ability to adapt smooth muscle tone to changes in transmural pressure. However, the intracellular signaling mechanisms involved in myogenic tone are not fully understood. Methods: Here, we investigated the relationship between mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3 kinase (PI3K) in isometric contraction and enzymatic activity using muscle strips from rats made hypertensive with aldosterone-analogue deoxycorticosterone acetate (DOCA) salts. Results: Changes in myogenic tone and intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) were different after physiological salt solution (PSS) in normotensive and hypertensive rats. The myogenic tone and quiescent phosphorylation induced by the PSS treatment were inhibited by 10 ${\mu}$M PD098059, an extracellular-regulated protein kinase 1/2 (ERK1/2) inhibitor, and 10 ${\mu}$M wortmannin, an inhibitor of PI3K, in hypertensive rats. Conclusion: The development of DOCA-induced hypertension is associated with altered isometric contractions and $[Ca^{2+}]_i$ via changes in activation of ERK1/2 and PI3K after DOCA-salt treatment. Therefore, ERK1/2 and PI3K activity affect hypertension and may be suitable targets for physical therapy in cardiovascular disease.

• 대한물리치료과학회지
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• 제13권2호
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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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• 제29권11호
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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.

• 대한물리치료과학회지
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• 제13권2호
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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.

• 대한물리치료과학회지
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• 제10권2호
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• pp.199-207
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• 2003

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 antiliypertensive 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 normal volunteer. The heart weight, the tickness of vascular wall, collagen fiber and the systolic blood pressure were significantly increased in ADHR than that in NSR. The required time of PSS-induced resting tone and the phosphorylation of stress-activated protein kinase/c-Jun N-terminal protein kinase(SAPK/JNK) were significantly increased in ADHR than that in NSR. However, the Kv currents were significantly decreased in ADHR than that in NSR. The current of 1 Hz continue type of SSP electrical stimulation significantly decreased in excretion of urine aldosterone from normal volunteer. These results suggest that the development of aldosterone analogue-induced hypertension is associated with changed heart weight, content of collagen fiber, tickness of vascular wall, blood pressure, resting tone, voltage-dependent K+ current(Kv) and phosphorylation of SAPK/JNK, which directly affects blood pressure. Therefore the hypertension is a risk factor on cerebrovascular disease. Moreover, These results suggest that the SSP electrical stimulation, especially current of 1 Hz continue type, significantly regulates excretion of urine aldosterone from volunteer.