• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.315-320
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• 1999

Molecular regulation of the renin-angiotensin system (RAS) was investigated in deoxycorticosterone acetate (DOCA)-salt hypertension. The expression of renin, angiotensinogen and angiotensin II receptor genes in the kidney and liver was determined by Northern blot analysis in rats which were made DOCA-salt hypertensive over the period of 2 or 4 weeks. Along with the hypertension, renin mRNA was decreased in the remnant kidney. The expression of angiotensinogen gene was not significantly altered in the kidney, but was significantly decreased in the liver. The expression of angiotensin II receptor gene was increased in the kidney, while it remained unaltered in the liver. The duration of hypertension did not affect the altered gene expression. It is suggested that the components of RAS are transcriptionally regulated in DOCA-salt hypertension in a tissue-specific manner.

• The Korean Journal of Physiology and Pharmacology
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• 제4권1호
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• pp.55-61
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• 2000

The present study was conducted to investigate the possible role of the sympathetic nervous system in two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension. 2K1C and DOCA- salt hypertension were made in Sprague-Dawley rats. Four weeks after induction of hypertension, systolic blood pressure measured in conscious state was significantly higher in 2K1C $(216{\pm}18\;mmHg)$ and DOCA-salt $(205{\pm}29\;mmHg)$ groups than that in control $(128{\pm}4\;mmHg).$ The third branches (＜300 ${\mu}m$ in outer diameter) of the mesenteric artery were isolated and cut into ring segments of $2{\sim}3$ mm in length. Each ring segment was mounted in tissue bath and connected to a force displacement transducer for measurement of isometric tension. The arterial rings were contracted by application of norepinephrine (NE) in a dose-dependent manner. The amplitude of the NE-induced contraction of the vessels was significantly larger in hypertension than in control. The NE-induced contraction was significantly enhanced by neuropeptide Y (NPY) in hypertension. Reciprocally, NPY-elicited vasocontraction was increased by NE in hypertension. These results suggest that the sympathetic nervous system contributes to the development of 2K1C and DOCA-salt hypertension.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.455-460
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• 1998

The present study was aimed at investigating whether the development of hypertension is related with an altered expression of nitric oxide synthases (NOS) in the kidney. By Western blot analysis, the expression of bNOS and ecNOS isoforms was determined in the kidney of deoxycorticosterone acetate (DOCA)-salt and two-kidney, one clip (2K1C) rats. In DOCA-salt hypertension, the expression of both bNOS and ecNOS was decreased, along with tissue contents of nitrites. In 2K1C hypertension, the nitrite content of the clipped kidney was decreased along with ecNOS levels, whereas neither the nitrite content nor the expression of NOS isoforms was significantly altered in the contralateral non-clipped kidney. These results suggest that the development of hypertension is associated with an altered renal expression of NOS and nitric oxide generation in DOCA-salt and 2K1C rats.

• 동의생리병리학회지
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• 제21권5호
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• pp.1176-1184
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• 2007

Chunmagudeungeumgamibang(CGE) has been used for many years as a therapeutic agent for acute stage of cerebrovascular disease and hypertension in oriental medicine. But the effect of CGE on hypertension and vascular system is not well-known. This study was done to investigate the effects of CGE on hypertension. The results were obtained as follow : CGE showed a safety in cytotoxicity and toxicity of liver. CGE showed scavenging activity on DPPH free radical. CGE showed the inhibitory effect on ROS and ACE. CGE significantly decreased the blood pressure and pulse in DOCA-salt hypertensive rat. CGE significantly decreased the levels of aldosterone in DOCA-salt hypertensive rat. CGE significantly decreased the levels of dopamine, epinephrine in DOCA-salt hypertensive rat. CGE significantly decreased the levels of potassium and chloride in DOCA-salt hypertensive rat. CGE significantly increased the levels of calcium in DOCA-salt hypertensive rat. These results suggest that CGE might be effective in treatment and prevention of hypertension

• The Korean Journal of Physiology
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• 제28권2호
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• pp.191-196
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• 1994

Captopril, an inhibitor of angiotensin converting enzyme, is also known to inhibit the degradation of bradykinin. We examined the effects of intracerebroventricular (ICV) captopril on the central pressor response to bradykinin in normotensive, 2-kidney, 1 clip Goldblatt (GHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Captopril (1 mg) and bradykinin (5 nmol) were administered into the right lateral cerebral ventricle, and blood pressure and heart rate were continuously monitored throughout the experiment. ICV captopril alone did not affect the blood pressure within 10 minutes but it significantly augmented the central pressor response to bradykinin in GHR. On the contrary, captopril was without effect on the pressor response to bradykinin in normotensive and DOCA-salt rats. These findings indicate that endogenous kinins are not critical in regulating arterial pressure in normotensive and DOCA hypertensive rats. However, in GHR, an enhanced activity of the brain kallikrein-kinin system in maintaining the high blood pressure is suggested.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제4권5호
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• pp.379-383
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• 2000

Pathophysiological implications of the vascular nitric oxide (NO)/cGMP pathway in hypertension were investigated. Sprague-Dawley rats were made deoxycorticosterone acetate (DOCA)-salt hypertensive for six weeks. The protein expression of endothelial constitutive NO synthase (ecNOS) and the tissue content of NO were determined in the thoracic aorta. The protein expression and catalytic activity of soluble guanylyl cyclase (GC) were also determined. Systolic blood pressure measured on the day of experiment was significantly higher in the experimental group than in the control. The hypertension was associated with decreases in the vascular tissue content of NO metabolites, concomitantly with the expression of ecNOS proteins. The protein expression of GC was not affected, while its catalytic activity was significantly decreased in hypertension. These results indicate that the high blood pressure is associated with a decreased activity of vascular NO/cGMP pathway in DOCA-salt hypertension.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제5권3호
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• pp.253-258
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• 2001

The present study was aimed to examine whether the expression of renin is associated with that of cyclooxygenase-2 (COX-2) in the kidney. Male Sprague-Dawley rats were made two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertensive, to stimulate or to inhibit the endogenous renin-angiotensin system, respectively. The expression of renin and COX-2 mRNA was determined in the cortex of the kidney by reverse transcription-polymerase chain reaction. 2K1C hypertensive rats showed an increased expression of renin as well as of COX-2 in the clipped kidney. The expression of renin was decreased in parallel with that of COX-2 in the contralateral non-clipped kidney. Removal of the renal arterial clip reversed the expression of both genes, along with the blood pressure, to the control level. On the other hand, DOCA-salt hypertension was associated with parallel decreases of renin and COX-2 expression. These results indicate that renin and COX-2 genes are coordinately expressed in the kidney.

• 약학회지
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• 제31권2호
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• pp.82-91
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• 1987

The effect of neurotoxic compound 6-hydroxydopamine (6-OHDA) on the change in blood pressure and contractile response of Vas deference by centrally acting agents has been studied in normal and DOCA-salt induced hypertensive rats. The treatment of neonatal rats with 6-OHDA (2$\times$100mg, 250mg Kg$^{-1}$s.c) significantly inhibited the antihypertensive and relaxant effects of Vas deference of clonidine(100$\mu\textrm{g}$ Kg$^{-1}$iv.). The simultaneous administration of desipramine with clonidine into neonatal rats decreased the antihypertensive response of clonidine although treated did not affect the relaxative response of Vas deference. Furthermore, the antihypertensive and relaxant responses of clonidine were reduced by the neonatal rats with 6-OHDA regardless of the administration of desipramine. When neonatal rats were administered with 6-OHDA, the development of DOCA-salt hypertension was prevented. These results suggest that 6-OHDA, clonidine and desipramine hada significant effect on the development and the inhibition of central hypertension mediating the central adrenergic neuron due to their affinity to the central nervous system.