• The Korean Journal of Physiology and Pharmacology
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• v.6 no.2
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• pp.121-125
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• 2002

The pathophysiological implications of aldosterone and adrenomedullin in the cardiac ventricular hypertrophy were examined. Male Sprague-Dawley rats were treated with deoxycorticosterone acetate (DOCA)-salt and monocrotaline (MCT) to selectively elicit left and right ventricular (LV, RV) hypertrophy, respectively. The mRNA expression of aldosterone synthase and adrenomedullin in LV and RV was determined by reverse transcription-polymerase chain reaction. The expression of aldosterone synthase and adrenomedullin was increased in LV, while not altered significantly in RV of DOCA-salt-treated rats. On the contrary, the expression was not significantly altered in LV, but increased in RV of MCT-treated rats. The enhanced expression of aldosterone synthase may be causally related with the development of ventricular hypertrophy, and the increased expression of adrenomedullin may act as a counter-regulatory mechanism.

• 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 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.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.3
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• pp.147-151
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• 2004

The present study was undertaken to determine the regulation of heat shock proteins (HSP) in the kidney in hypertension. Two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertension was induced in male Sprague-Dawley rats. At weeks 1 and 4 after inducing the hypertension, the expression of HSP70, HSP32 and HSP25 was determined in the kidney by Western blot analysis. In 2K1C hypertension, the expression of HSP70, HSP32 and HSP25 was increased in the clipped kidney at both weeks 1 and 4. However, in the contralateral kidney, their expression was not significantly altered at week 1, but increased at week 4. In DOCA-salt hypertension, the expression of HSP remained unaltered in the remnant kidney at week 1, but significantly increased at week 4. These results indicate that HSP are differentially regulated in the kidney according to the duration and the model of hypertension.

• The Journal of Korean Physical Therapy
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• v.20 no.4
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.504-510
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• 2007

Kamicheonmagudeungeum(KCGE), a traditional herbal medicine, has been used as a therapeutic agent for the treatments of acute stage of hypertension. We evaluated the effects of KCGE on hypertension induced by DOCA-salt in rats. The systolic blood pressure and pulse rate significantly lowered by oral administration with KCGE. The levels of plasma hormones including dopamine, epinephrine and norepinephrine, and serum electrolyte were also reduced in KCGE treated rats. In addition, the production of reactive oxigen species (ROS) were greatly decreased by the treatment with KCGE in cultured bovine endothelial cells and angiotensine converting enzyme (ACE) activites were also inhibited by KCGE in a dose dependent manner. This study indicated that KCGE is a safe and effective treatment for hypertension.

• The Korea Journal of Herbology
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• v.24 no.4
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• pp.69-75
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• 2009

Objectives : To access the safety and efficacy of Black Ginseng (BG), a traditional herbal medicine on hypertension, we examined various parameters involved in the pathogenesis of hypertension. Methods : We made deoxycorticosterone acetate (DOCA;25 mg/kg/3times/weeks for 3 weeks)-induced hypertension Sprague-Dawley (SD) rats. And experiment group was treated with extract of black ginseng (BG;200 mg/kg/day). Results : In results, the weight of experiment group treated with BG was increased compared with normal and control group. And the heart and lung weights of experiment group were decreased compared with control group. The blood pressure and pulse rate of group treated with BG were significantly decreased compared with control group. In addition, BG greatly reduced the levels of aldosterone. These results suggested that BG has suppressive effects on hypertension, and BG has potential as a safe and effective therapeutics for hypertension. Conclusions : The present data show evidences on anti-hypertension activity of BG in an experimental animal system, which can provide further insights into the development of anti-hypertension therapeutic agents.

• The Journal of Korean Physical Therapy
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• v.20 no.3
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• pp.61-68
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• 2008

Purpose: Protein kinase C (PKC) is a member of a family of serine/threonine kinases that are activated by diacylglycerol (DG) and PKC stimulants. PKC play a key role in signal transduction, including muscle contraction, cell migration, apoptosis, cell proliferation and differentiation. However, the mechanism relating mitogen-activated protein kinases (MAPKs) and PKC, especially in the volume-dependent hypertensive state, remains unclear. Methods: In the present study, I investigated the relationship between PKC and MAPKs for isometric contraction, PKC translocation, and enzymatic activity from normotensive sham-operated rats (NSR) and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive rats (ADHR). Results: Systolic blood pressure was significantly increased in ADHR than in NSR. Physiological salt solution (PSS)-induced resting tension and the intracellular $Ca^{2+}$ concentration ([$Ca^{2+}{_i}$]) were different in the ADHR and NSR. The expression of PKC$\alpha$, PKC$\beta$II, PKC$\delta$, PKC$\varepsilon$ and PKC$\xi$ were different between the cytoplasmic and membranous fractions. However, expression of the PKC isoforms did not differ for the ADHR and NSR. The use of 12-deoxyphorbol 13-isobutyrate (DPB, a PKC stimulant) induced isometric contraction in $Ca^{2+}$-free medium, which was diminished in muscle strips from ADHR as compared to NSR. Increased vasoconstriction and phosphorylation induced by the use of 1 ${\mu}$M DPB were inhibited by treatment with 10 ${\mu}$M PD098059 and 10 ${\mu}$M SB203580, inhibitors of extracellular-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK from ADHR, respectively. Conclusion: These results suggest that the development of aldosterone analogue-induced hypertension is associated with an altered blood pressure, resting tension, [$Ca^{2+}{_i}$], and that the $Ca^{2+}$-independent contraction evoked by PKC stimulants is due to the activation of ERK1/2 and p38 MAPK in volume-dependent hypertension. Therefore, it is suggested that PKC activity affects volume-dependent hypertension and the need to develop cardiovascular disease-specialized physical therapy.

• YAKHAK HOEJI
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• v.31 no.5
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• pp.308-314
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• 1987

In cardiovascular disease the flow adaptation of erythrocytes can be affected by reduced shear stresses and metabolic influences on red cell fluidity as a consequence of tissue hypoxia. In addition there are indications that risk factors of cardiovascular diseases are able to decrease the intrinsic red cell deformability. Erythrocyte deformability was studied by the filtration technique of Reid et al. to investigate the relationship between blood pressure chances and erythrocyte deformability. In this experiment normotensive rats, spontaneously and DOCA-salt treated hypertensive rats were used. Erythrocyte deformability was significantly reduced by blood pressure elevation in hypertensive rats but was not fully recovered by normalization of blood pressure after antihypertensive drug treatment. Therefore other factors than blood pressure may be involved in erythrocyte deformability reduction during blood pressure elevation.

• 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.