• The Korean Journal of Physiology
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• v.28 no.2
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• pp.169-179
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• 1994

The effect of extracellular and intracellular pH on vascular tone and $^{45}Ca$ uptake were investigated in aortic strips and dispersed single aortic smooth muscle cells of spontaneously hypertensive rats (SHR) and aged-matched Wistar-Kyoto rats (WKY). The contraction produced by a change of extracellular pH (pHo) in the range of $6.5{\sim}8.3$ was estimated by comparison with the level of vascular tone at pH 7.4. Contraction was induced below pHo 6.5 in WKY, pHo 7.1 in SHR, and over pHo 8.0 on both strains. The amplitude of contraction induced by high pHo (over pHo 7.7) was similar in SHR and WKY, but that induced by low pHo (below pHo 7.1) in SHR was greater than that in WKY. Either high pHo- or low pHo-induced contractions in WKY and SHR were not induced in the Ca-free Tyrode's solution and were induced by the addition of Ca. $^{45}Ca$ uptake increased progressively as pHo was increased from 6.8 to 8.1 in the single aortic smooth muscle cells of WKY and SHR. $NH_4Cl$ induced a gradually developing contraction in a dose-dependent manner $(5\;mM{\sim}30\;mM)$ and the removal of $NH_4Cl$ induced transient contraction was followed by profound relaxation in the aortic rings of both strains. The contractions induced by $NH_4Cl$ or by the removal of $NH_4Cl$ in SHR were significantly greater than that in WKY. These contractions were not induced in Ca-free Tyrode's solution. $^{45}Ca$ uptake was increased by $NH_4Cl$ (20 mM) and was not changed by the removal of $NH_4Cl$ (20 mM) in the aortic strips of WKY and SHR. As a summary of above results, the vascular tone of SHR was more sensitive to the change pHi and pHo than that of WKY. The contractions induced by change of extracellular or intracellular pH depended on extracellular Ca in the aorta of SHR nnd WKY. However, the Ca uptake was in accord with the changes of contraction but increase in contraction by low pH was not accompanied by an increase in Ca uptake in both strains.

• Korean Journal of Oriental Medicine
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• v.12 no.3 s.18
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• pp.59-67
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• 2006

Aims: Acupuncture has been used for the treatment of essential hypertension, but the efficacy and the mechanism of acupuncture in prevention of hypertension are still unclear. We tested the hypothesis that electroacupuncture (EA) applied to Baekhoe (GV20) changes NO/NOS system during development of hypertension in spontaneously hypertensive rats (SHR), and thereby causes the delay of development of hypertension in SHR. Methods: The male SHR rats in the developmental stages of hypertension (7-8 weeks) were randomly divided into three groups (control group, GV20 acupuncture group, and tail acupuncture group). And the age matched Wistar Koyto Rats (WKY) were randomly divided into two groups (nagative control, GV20 acupuncture group). EA treatments (10Hz, 1mA, 0.1ms) were carried out for 25 min/day for five consecutive days. The systolic blood pressure (SBP) was determined in conscious rats by the tail-cuff method using automatic BP mornitoring system. We investigated the activations of inducible NO synthase (iNOS) in nuclei of solitary tract (NTS) and rostral ventrolateral medulla (RVLM) of SHR by the western blotting method. Results: The SBP after the termination of EA stimulation applied to the GV20 was stabilized at $169.14{\pm}3.67$ mmHg which is lower value than that of the control group. The SBP of control group was elevated to $178.14{\pm}3.49$ mmHg. In addition, we evaluated NOS activity as well as iNOS protein expression of NTS and RVLM in both of SHR and WKY. The iNOS activity in NTS was significantly higher in SHR than in WKY. Furthermore, the iNOS activity of NTS showed significant decreases in EA groups compare to that of non treated SHR group. Although iNOS expression of RVLM showed non significant changes between SHR and WKY, EA significantly enhanced the iNOS expression in SHR. Our data support the hypothesis that delayed development of hypertension and altered iNOS expression of NTS and RVLM by EA stimulations in SHR rats. Conclusions: The findings demonstrate that acupuncture can change NO/NOS system in NTS and RVLM, and exert beneficial role on development of hypertension.

• Toxicological Research
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• v.6 no.1
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• pp.75-88
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• 1990

The characteristics of dopamine uptake, D-1 and D-2 receptors after acute and subacute cocaine administration were determind in striatum from WKY and SHR. Cocaine was administered either acutely (40 mg/kg, s.c.) or twice daily (20 mg/kg, s.c.) for 3 and 7 days in 9-wk old WKY and SHR. Rats were sacrificed 30 min, 2 or 24 h after the single injection and 18 h after the last administration to the subacutely treated group. The changes in dopamine uptake, dopamine uptake sites, D-1 and D-2 receptors were determined using $(^3H)$dopamine, $(^3H)$-GBR-12935, $(^3H)$SCH-23390 and $(^3H)$sulpiride, respectively. In acutely treated rats, significant increases in $V_{max}$of dopamine uptake were observed 30 min after the cocanine injection in both strains without changes in $K_m$ values. The in vitro $IC_{50}$for cocaine was significantly decreased 30 min in WKY and 2 h in SHR. However, that for in vitro GBR-12909 was significantly increased 30 min and 2 h in both strains. Also densities of $(^3H)$-GBR-12935 binding sites were significantly increased 30 min and 2 h without changes in their $K_d$. Significant increases in D-2 receptor density were observed 30 min, 2 or 24 h after acute injection in both strains without changes in their affinities. The density of D-1 receptor was significantly decreased 30 min after the injection in WKY, but not in SHR. In subacutely treated rats, a significant increase in $K_m$ of dopamine uptake was observed in 7-day treated SHR. The in vitro $IC_{50}$fot GBR-12909 was significantly increased in 3-day treated WKY. The density of D-1 receptors was significantly increased in 3- and 7-day treated WKY, but not in SHR. The affinity of both binding sites remained unchanged. The results suggest that cocanine administration alters dopamine uptake, characteristics of dopamine uptake sites and dopamine receptor binding characteristics in rat brain. Furthermore, D-1 and D-2 dopamine receptors appear to be differently regulated.

• Preventive Nutrition and Food Science
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• v.6 no.1
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• pp.43-50
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• 2001

The effects of cardiac ischemia-reperfusion and $\beta$-adrenergic stimulation on metabolic function and energetics were investigated in Lan gendorff-perfused spontaneously hypertensive rat (SHR) hearts. Sarcoplasmic reticulum {TEX}$Ca^{2+}${/TEX}-dependent ATPase and cardiac lactate dehydrogenase (LDH) are additionally studied. The perfusion medium (1.0 mM {TEX}$Ca^{2+}${/TEX}) contained 5 mM glucose(+5 U/L insulin) and 2 mM pyruvate as substrates. Global ischemia was induced by reducing perfusion pressure of 100 to 40 cm {TEX}$H_{2}${/TEX}O, followed by 20 min reperfusin. Isoproterenol (ISO, 1$\mu$M) was infused for 10 min. Coronary vascular resistance and myocardial oxygen consumption ({TEX}$MVO_{2}${/TEX}) of SHR were increased in parallel with enhanced venous lactate during ischemia and reperfusion compared to those of Sprague Dawley (SD) hearts. Although ischemia-induced increase in venous lactate and combined adenosine plus inosine was abolished, coronary vasodilation produced in SD during reperfusion. In SHR, depressed reactive hyperemia was associated with a fall in cardiac ATP and CrP/Pi ratio and a rise in intracellular lactate/Pyruvate ratio. On the other hand, ISO produced coronary functional hyperemia and an increase in {TEX}$MVO_{2}${/TEX}. However, these responses were less than those in SHR hearts. The ATPase activity of SHR was attenuated in free {TEX}$Ca^{2+}${/TEX} concentrations used under basal condition and with ISO compared to that of SD. Venous lactate output and cardiac LDH activity were augmented in SHR as influenced by ISO. These results demonstrate that coronary reactive and functional hyperemia was dpressed in SHR, which cold be explained by alterations in the cytosolic phosphorylation potential and the cytosolic redox state manipulated by LDH, and by abnormal free calcium handling.

• Nutrition Research and Practice
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• v.6 no.4
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• pp.315-321
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• 2012

We tested the effects of dietary intake of freeze-dried Korean traditional fermented cabbage (generally known as kimchi) with varying amounts of sodium on blood pressure and cardiac hypertrophy in spontaneously hypertensive rats (SHRs). Wistar-Kyoto rats (WKY), as a control group, received a regular AIN-76 diet, and the SHRs were divided into four groups. The SHR group was fed a regular diet without kimchi supplementation, the SHR-L group was fed the regular diet supplemented with low sodium kimchi containing 1.4% salt by wet weight, which was provided in a freeze-dried form, the SHR-M group was supplemented with medium levels of sodium kimchi containing 2.4% salt, and the SHR-H group was supplemented with high sodium kimchi containing 3.0% salt. Blood pressure was measured over 6 weeks, and cardiac hypertrophy was examined by measuring heart and left ventricle weights and cardiac histology. SHRs showed higher blood pressure compared to that in WKY rats, which was further elevated by consuming high sodium containing kimchi but was not influenced by supplementing with low sodium kimchi. None of the SHR groups showed significant differences in cardiac and left ventricular mass or cardiomyocyte size. Levels of serum biochemical parameters, including blood urea nitrogen, creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sodium, and potassium were not different among the groups. Elevations in serum levels of aldosterone in SHR rats decreased in the low sodium kimchi group. These results suggest that consuming low sodium kimchi may not adversely affect blood pressure and cardiac function even under a hypertensive condition.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.336-343
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• 1997

The purpose of the present study was to address whether the in vivo noradrenergic neural activities in the locus coeruleus are related to the development of hypertension. Two groups of the animals were prepared, 1) young SHR and 2) age-matched normotensive control, WKY. At the age of 6 weeks, blood pressure and the releases of NE and DOPEG from the locus coeruleus in young SHR and WKY were measured by in vivo microdialysis at two different conditions; 1) normal and 2) elevated state of blood pressure by systemically injected phenylephrine. Basal releases of NE and OOPEG from the locus coeruleus were $0.415 \pm$0.089 pg/20 min and $1.311 \pm0.293$ pg/20 min in SHR and $0.204\pm0.078$ pg/20 min and $1.472\pm 0.365$ pg/20 min in WKY The basal release of NE of SHR was significantly greater than that of WKY. Phenylephrine treatment caused elevation of blood pressure in both SHR and WKY in dose-dependent manner. Following phenylephrine injection, the releases of NE and DOPEG from the locus coeruleus of SHR were significantly decreased, whereas there was no significant changes of NE in WKY. The results from the present study suggests that the noradrenergic nervous system in the locus coeruleus may contribute as one of the triggering factors for the expression of hypertension in young SHR.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.21-31
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• 1996

To investigate the mechanisms of increased endothelium-dependent contraction by acetylcholine in hypertensive rats, the relationship between endothelium-dependent contraction by acetylcholine and blood pressure was studied in spontaneously hypertensive rats (SHR), one-kidney, one clip Goldblatt hypertension (1K,1C-GBH) rats, and Wistar-Kyoto rats (WKY). SHR were treated orally with enalapril or nicardipine in order to prevent development of hypertension or suppress the developed hypertension. 1K,1C-GBH rats were made by renal artery stenosis with contralateral nephrectomy in 8 week-WKY. 1. Endothelium-dependent contractions by acetylcholine $(10^{-6}{\sim}10^{-5}\;M)$ in SHR were significantly greater than those in WKY. 2. Chronic treatment with enalapril or nicardipine reduced the endothelium-dependent contraction in SHR 3. The degree of reduction of endothelium-dependent contraction was greater in SHR which was prevented from developing hypertension than in SHR of which high blood pressure was suppressed. 4. In aortic rings from 1K,1C-GBH rats, endothelium-dependent contractions by acetylcholine were augmented as compared with WKY. 5. There is good relationship between the value of blood pressure and magnitude of endothelium-dependent contraction. Thus, it is suggested that increased endothelium-dependent contraction in hypertensive rats may he due to the high blood pressure and endothelium-dependent contraction may not be a cause of the initiation of hypertension in SHR.

• The Korean Journal of Physiology
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• v.24 no.2
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• pp.319-329
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• 1990

Effects of atrial natriuretic peptide (ANP) on blood pressure, plasma lenin activity, aldosterone and renal excretion were compared in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar rats fed low, medium or high sodium diet (2, 10, 25 mmol NaCl/100g diet) for 6 weeks. ANP infusion (380 ng/kg/min for 20 min) produced reductions in blood pressure, plasma renin activity, and aldosterone level, but marked increases in hematocrit, urine flow, and excretions of sodium and potassium. The low sodium group showed a significantly enhanced aldosterone lowering effect of ANP than the high sodium group. However, three salt groups showed no difference in effects of ANP on blood pressure, plasma renin activity, hematocrit and diuresis. Natriuretic response to ANP was significantly greater in the high salt-than in the low sait-SHR, but was not different between the Wistar salt groups. There were strain differences in effects of ANP: SHR showed greater responses of blood pressure and natriuresis than Wistar rats. Above results indicate that aldosterone-lowering and natriuretic effects of ANP were modifed by different dietary sodium intakes. However, blood pressure- and renin-lowering, or diuretic effects of ANP were not affected by dietary sodium intakes. The mechanisms whereby dietary sodium intakes alter the effects of ANP in the pathogenesis of hypertension are not clear.

• The Journal of Internal Korean Medicine
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• v.32 no.3
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• pp.345-360
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• 2011

Objectives : This study was examined to investigate the effects of Cheonmagudeng-um gagam (CGG) extract on spontaneous hypertension. Methods : For the study of CGG, we divided rats into three groups. The normal group was Wister Kyoto rats (WKY). The control group was spontaneously hypertensive rats (SHR). The treatment group was SHR which were administered CGG extract (SHR-CGG). SHR-CGG were orally administered CGG extract that was diluted in distilled water at the various concentrations for 4 weeks (234.5 mg/kg) and SHR were orally administered the same dosage of plain distilled water as SHR-CGG. Then we measured anti-oxygen effects, ACE inhibitory activity, weight of heart and kidney, blood pressure, heart rate, plasma aldosterone, electrolyte, creatinine, uric acid, BUN, and observed the cortex of the cardiac muscle, kidney, and adrenal gland. Results : CGG increased DPPH scavenging activity and SOD similar activity depending on the concentration. CGG significantly decreased ROS, TNF-${\alpha}$, IL-6, IL-$1{\beta}$, heart weight, blood pressure, heart rate, aldosterone, and BUN in SHR. CGG increased ACE inhibition activity depending on the concentration. CGG inhibited the heart, kidney and adrenal gland tissue injury that is caused by hypertension. Conclusions : These results suggest that CGG is effective in treatment and prevention of hypertension.

• Advances in Traditional Medicine
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• v.8 no.4
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• pp.430-439
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• 2008

Chungpaesagan-tang (CPSGT) is most frequently used to treat ischemic brain injury in tradition Korean medicine. Clinically, cerebral ischemia is likely to be accompanied by preexisting or complicating disease. However, animal models used to examine the effects of herbal medicines on cerebral ischemia have not given this issue sufficient consideration. The present study was undertaken to determine the effects of CPSGT on focal cerebral ischemia in normal and SHR rats subjected to transient middle cerebral artery occlusion (MCAO). Animals were divided into four groups: Normal (Sprague-Dawley) rats subjected to MACO (the NC+MCAO group), normal rats subjected to MCAO and then administered CPSGT (NC + MCAO + CP), SHR rats subjected to MCAO (SHR + MCAO), and SHR rats subjected to MCAO and then administered CPSGT (SHR + MCAO + CP). MCAO was performed using the intraluminal method. CPSGT was administrated orally twice (1 and 4 h) after MCAO. All animals were sacrificed at 24 h postoperatively. Brain tissues were stained with hematoxylin & eosin, to examine the effect of CPSGT on ischemic brain tissues. In addition, changes in TNF-$\alpha$ expression in ischemic areas were examined by immunostaining. CPSGT was found to significantly reduce infarction areas in normal and SHR rats and infarction volumes in SHR rats. Similarly, CPGST markedly increased neuron numbers and sizes in all treated groups, except cell sizes in SHRs. Furthermore, CPSGT reduced TNF-$\alpha$ expression in MCAO administered SHR rats. The findings of the present study suggest that CPSGT effectively ameliorates neuron damage caused by MACO-induced cerebral ischemia, and that it has a significant neuroprotective effect after cerebral ischemia in SHR.