• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.547-553
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• 1997

It has been known that activation of tyrosine kinases is involved in signal transduction. Role of the tyrosine kinase in vascular smooth muscle contraction was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Male Sprague-Dawley rats underwent uninephrectomy, one week after which they were subcutaneously implanted with DOCA (200 mg/kg) and supplied with 1% NaCl and 0.2% KCl drinking water for $4{\sim}6$ weeks. Control rats were treated the same except for that no DOCA was implanted. Helical strips of carotid arteries were mounted in organ baths for measurement of isometric force development. Genistein was used as a tyrosine kinase inhibitor. Concentration-response curves to 5-hydroxytryptamine (5-HT) shifted to the right by genistein in both DOCA-salt hypertensive and control rats. Although the sensitivity to genistein was similar between the two groups, the maximum force generation by 5-HT was less inhibited by genistein in arteries from DOCA-salt hypertensive rats than in those from controls. Genistein-induced relaxations were attenuated in arteries from DOCA-salt rats. Genistein affected the contraction to phorbol 12, 13-dibutyrate (PDBu) neither in DOCA-salt nor in control arteries. These observations suggest that tyrosine kinase is involved in 5-HT-induced vascular contraction, of which role is reduced in DOCA-salt hypertension.

• 대한한방내과학회지
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• 제29권3호
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• pp.641-656
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• 2008

This study was done to investigate the effect of Gamichungyeoldodam-tang (GCDT) in DOCA-salt induced hypertensive rats. The results were obtained as follows : GCDT showed safety against cytotoxicity and toxicity in the liver and the kidney. GCDT showed an inhibitory effect on ACE. GCDT significantly decreased the heart rate and the blood pressure in DOCA-salt induced hypertensive rats. GCDT significantly decreased the levels of aldosterone in DOCA-salt induced hypertensive rats. GCDT significantly decreased the levels of dopamine, norepinephrine, and epinephrine in DOCA-salt induced hypertensive rats. GCDT significantly decreased the levels of chloride in DOCA-salt induced hypertensive rats. These results suggest that GCDT might be effective in treatment of hypertension.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.171-176
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• 1993

Purpose of the present study was to clarify the role of noradrenergic neural activities in hypothalamus for either triggering or maintaining hypertension in deoxycorticosterone (DOCA)-salt hypertensive rats. Two groups of animals were prepared: 1) normotensive Wistar rats and 2) DOCA-salt induced hypertensive rats. Voltage dependent $^{45}Ca^{++}$ uptake, endogenous norepinephrine release, and the catecholamine content in the hypothalamus of DOCA-salt hypertensive and normotensive Wistar rats were compared. Animals at 4, 6 and 16 week-old of two groups were sacrificed by decapitation and hypothalamus was dissected out. Voltage dependent calcium uptake and norepinephrine release were determined from hypothalamic synaptosomes either in low potassium or high potassium stimulatory condition by using $^{45}Ca^{++}$ isotope and HPLC-ECD technique. Degrees of voltage dependent $^{45}Ca^{++}$ uptake and norepinephrine release in hypothalamic synaptosomes of 16-week-old DOCA-salt hypertensive rats were significantly greater than those of age matched normotensive control rats. The norepinephrine and dopamine contents of hypothalamus were about the same in two groups of animals. These results suggest that the alteration of evoked norepinephrine release related to calcium uptake in hypothalamus may play a role in the maintenance of hypertension in DOCA-salt hypertensive rats.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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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.

• 동의생리병리학회지
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• 제22권5호
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• pp.1240-1249
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• 2008

Kamigingansikpung-tang(KGST) 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 KGST on hypertension and vascular system is not well-known. This study was done to investigate the effects of KGST on hypertension. The results were obtained as follow: KGST showed scavenging activity on DPPH free radical. KGST showed the inhibitory effect on ROS and ACE, and the accelerated SOD activity. KGST significantly decreased the blood pressure and pulse in DOCA-salt induced hypertensive rat. KGST significantly decreased the levels of aldosterone in DOCA-salt induced hypertensive rat. KGST significantly decreased the levels of dopamine, epinephrine in DOCA-salt induced hypertensive rat. KGST significantly decreased the levels of potassium(K+) and chloride(Cl-) in DOCA-salt induced hypertensive rat. KGST significantly decreased the levels of uric acid and creatine in DOCA-salt induced hypertensive rat. KGST has an effect on inhibiting cell damage of the heart, liver, kidney, and adrenal gland. results suggest that KGST might be effective in treatment and prevention of hypertension.

• 동의생리병리학회지
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• 제22권1호
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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 Chest Surgery
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• 제32권2호
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• pp.138-143
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• 1999

배경: 혈관 내피층에서 분비되어 평활근층 이완을 일으키는 물질의 본체는 산화질소(nitric oxide, NO)이며 NO synthase(NOS)에는 뇌형(brain NOS, bNOS), 내피세포형(endothelial constitutive NOS, ecNOS) 및 유도형 (inducible NOS, iNOS) 등 세 가지 동위효소가 있음이 알려져 있다. 고혈압은 혈관 내피층 기능 이상을 보임이 알려져 있으나 NOS 동위 효소의 변화를 포함한 세포내 기전은 아직 확실치 않다. 저자들은 고혈압 기전을 구명하기 위한 일환으로 고혈압 혈관에서 NOS 동위효소가 어떻게 변화되는가 조사하고자 하였다. 대상 및 방법: 흰쥐에서 two-kidney, one clip (2K1C) 고혈압과 deoxycorticosterone acetate(DOCA)-salt 고혈압을 일으켰다. 4주 뒤 고혈압이 일어난 것을 확인하고 적출 흉부 대동맥 표본에서 Western blot 분석에 의한 NOS 동위효소 발현 조사 및 비색법에 의한 조직내 산화질소 정량을 하였다. 결과: 2K1C 및 DOCA-salt 흰쥐에서 실험군은 각각의 대조군에 비해 유의하게 높은 혈압을 보였다. 두 고혈압군에서 모두 적출 대동맥 표본의 bNOS 및 ecNOS 단백 발현이 감소되었다. iNOS 단백은 DOCA-salt 고혈압에서 변화를 보이지 않으나 2K1C 고혈압에서는 역시 감소를 보였다. 혈관조직내 산화질소 함량은 두 고혈압에서 모두 유의하게 감소되었다. 결론: 2K1C 및 DOCA-salt 고혈압에서 혈관의 NOS 발현과 산화질소 함량이 감소되어 있으며 이는 고혈압의 유지 기전에 공헌하리라 추측되었다.

• Advances in Traditional Medicine
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• 제8권4호
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• pp.354-364
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• 2008

The present study was carried out to investigate the antihypertensive effect of a folklore herbal formulation (HF) (300mg/kg/day; p.o.) in deoxycorticosterone acetate (DOCA)-salt induced and fructose induced hypertensive rats. In DOCA model, DOCA (15 mg/kg, s.c., twice a week) was administered to unilateral nephrectomized rats for 4 weeks. In fructose model, drinking water was replaced with 10% fructose solution for 6 weeks to induce hypertension. Systolic blood pressure (BP) was measured once every week during the treatment schedule. After completion of treatment schedule, BP and vascular reactivity to various agonists like Noradrenaline, Adrenaline, Phenylephrine and Serotonin (5-hydroxytrptamine; 5-HT) were recorded in rats of both models. A cumulative concentration response curve of 5-HT was carried out in isolated rat fundus strip of the DOCA-salt induced and fructose induced hypertensive rats. The results tend to suggest that HF possesses antihypertensive activity.

• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.351-356
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• 1999

The present study was aimed at investigating whether the calcium current in the vascular smooth muscle (VSM) cells is altered in renal hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in Sprague-Dawley rats. Rats without clipping the renal artery or implanting DOCA were used as control for 2K1C and DOCA-salt hypertension, respectively. Four weeks after clipping, systolic blood pressure was significantly higher in 2K1C rats than in control $(192{\pm}24\;and\;119{\pm}4$ mmHg, respectively, n=16 each). DOCA-salt rats also showed a higher blood pressure $(180{\pm}15$ mmHg, n=18) compared with control $(121{\pm}6$ mmHg, n=14). VSM cells were enzymatically and mechanically isolated from basilar arteries. Single relaxed VSM cells measured $5{\sim}10\;{\mu}m$ in width and $70{\sim}150\;{\mu}m$ in length were obtained. VSM cells could not be differentiated in size and shape between hypertensive and normotensive rats under light microscopy. High-threshold (L-type) calcium currents were recorded using whole-cell patch clamp technique. The amplitude of the current recorded from VSM cells was larger in 2K1C hypertension than in control. Neither the voltage-dependence of the calcium current nor the cell capacitance was significantly affected by 2K1C hypertension. By contrast, the amplitude of the calcium current was not altered in DOCA-salt hypertension. These results suggest that high-threshold calcium current of the VSM cells is altered in 2K1C hypertension, and that calcium channel may not be involved in calcium recruitment of VSM in DOCA-salt hypertension.

• 동의생리병리학회지
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• 제20권6호
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• pp.1485-1496
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• 2006

Various kinds of related parameters on hypertension such as anti-oxygen effect, ACE, weight of body, hwart and kidney, blood pressure, heartbeat rates, contents of aldosterone, catecholamine, change rates, of plasma constituents, uric acid, BUN, creatinine were determined to verify the effects on hypertension by Kamisamul-tang (KSMT). And the results are concluded as follows. KSMT did not show any cytotoxicity at the range of concentration (1-250 ${\mu}g/m{\ell}$) on the human fibroblast cell (hFCs). KSMT decreased the production of reactive oxygen species (ROS) and DPPH generation depending on the concentration. KSMT significantly inhibited angiotensin converting enzyme(ACE) activity depending on the concentration compared with control. KSMT maintained body weight of body, heat and kidney nearly normal group in hypertensive rat induced by DOCA-salt. KSMT significantly blood pressure and heart beat rate compared with control in hypertensive rat induced by DOCA-salt. KSMT significantly decreased aldosterone, dopamine, norepineph- rine, epinephrine compared with control in hypertensive rat induced by DOCA-salt. KSMT significantly decreased the level of potassium and cloride compared with control wheareas increased that of calcium significantly in hypertensive rat induced by DOCA-salt. KSMT significantly decreased the level of uric acid and BUN compared with control in hypertensive rat induced by DOCA-salt. It is verified experimentally tat Kamisamultang(KMST) which has been used broadly as a clinical therapeutics in oriental medicine is effective for anti-hypertension mechanism. And it could be applied to develope the reliable prescriptions for anti-hypertension in the future.