• 대한수의학회지
• /
• 제45권4호
• /
• pp.537-544
• /
• 2005

We have examined distribution and expression of caveolin-3 (cav-3), one of three caveolin isoforms from 16-wks-old spontaneously hypertensive rats (SHR) compared with age-matched control wistar-kyoto (WKY) rats. The expression of cav-3 was increased, whereas expression of PKB/Akt and calcineurin (Cn) was not changed in cardiac tissues of SHR compared to WKY rats. Interestingly, expression of cav-3, PKB/Akt and Cn were decreased in plasma membrane fraction in SHR compared to WKY rats. In H9c2 cardiomyoblast cells treated with phenylephrine ($50{\mu}M$, 48hr) or isoproterenol ($10{\mu}M$, 48hr), the expression of cav-3 was markedly enhanced compared to nontreated cells. Upon immunofluorescence analysis, cav-3 was localized in plasma membrane of control H9c2 cells. However phenylephrine or isoproterenol treatment caused translocation of cav-3 to perinuclear region. These results suggest that cav-3 plays as positive regulators in the development of hypertrophy in cardiac tissues of SHR rats.

• 한국한의학연구원논문집
• /
• 제13권2호통권20호
• /
• pp.149-155
• /
• 2007

Objective : Using a spontaneously hypertensive rat (SHR) model of essential hypertension, this study investigated whether electroacupuncture (EA) could reduce early stage hypertension by examining whether EA increased nitric oxide (NO) levels in plasma, which compensates for elevated blood pressure (BP). Methods : EA was applied to the acupoint, Baekhoe (GV20), and to a non acupoint in the tail at 10 Hz and an intensity of 1 mA for 10 minutes on the first and fourth day of the week for three weeks under isoflurane anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY) rats, blood pressure was determined the day after EA treatment by the tail cuff method using an automatic BP monitoring system. We also measured NO concentration of blood serum in SHR and WKY. Results : Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower after 3 weeks of GV20 treatment than in non EA treated or non acupoint treated SHR rats. The NO level of plasma was significantly lower in hypertensive SHR than in normotensive WKY. EA prevented the augmentation of blood pressure, and also increased NO concentrations from $7.91{\pm}0.42$ ${\mu}M$ to $11.50{\pm}0.93$ ${\mu}M$ in SHR serum. Conclusions : We suggest that acupuncture may be an early intervention to delay the development of hypertension and enhance NO/NOS activity.

• The Korean Journal of Physiology
• /
• 제30권1호
• /
• pp.21-31
• /
• 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.

• 생명과학회지
• /
• 제22권5호
• /
• pp.665-670
• /
• 2012

이 연구는 자연발생고혈압쥐(SHR)의 혈압, 골격근에서의 혈관생성 및 혈관내피세포성장인자 발현(VEGF)에 미치는 지구성운동의 효과를 조사하였다. 5주령 SHR와 WKY는 무작위로 정상혈압군(WKY, Wistar-Kyoto rat, n=9), 고혈압통제군(SHR-C, SHR Control, n=9) 및 고혈압운동군(SHR-E, SHR Exercise, n=9)으로 각각 분류하였고, 지구성운동은 트레드밀을 이용하였다(12-20 m/min, 0% grade, 60 min/day, 5 days/wk, 16 wk). 수축기혈압은 지구성운동에 의해 효과적으로 감소되었다(SHR-E vs. SHR-C, $p$ <0.05). 골격근의 모세혈관밀도와 VEGF 단백발현은 고혈압통제군(SHR-C)이 정상혈압군(WKY)보다 모두 감소되었으나, 지구성운동(SHR-E)이 고혈압통제군(SHR-C)에 비해 모두 증가되었다. 이러한 결과들은 지구력운동 트레이닝이 SHR 골격근의 VEGF 단백발현의 증가를 통해 모세혈관밀도를 향상시키고, 이러한 모세혈관밀도의 향상이 SHR의 혈압상승을 억제할 수 있다는 것을 의미한다.

• Archives of Pharmacal Research
• /
• 제12권2호
• /
• pp.128-134
• /
• 1989

$Na^+-Ca^{2+}$ exchange process in sarcolemmal vesicles isolated from mesenteric arteries of Wistar-Kyoto normotensive(WKY) and spontaneously hypertensive rats(SHR) was investigated. The sarcolemmal fractions isolated after homogenization and sucrose density gradient centrifugation were enriched with 5'-nucleotidase and ouabain sensitive, $K^+-dependent$ phosphatase activities. When the vesicles were loaded with $Na^+$, a time dependent $Ca^{2+}$ uptake was observed. However, very little $Ca^{2+}$ uptake was observed when the vesicles were loaded with $K^+$, or $Ca^{2+}$ uptake of the $Na^+-loaded$ vesicles was carried out in high sodium medium so that there was no sodium gradient. When the vesicles loaded with $Ca^{2+}$ by $Na^+-Ca^{2+}$ exchange were diluted into potassium medium containing EGTA, $Ca^{2+}$ was rapidly released from the vesicles. $Na^+-dependent\;Ca^{2+}$ uptake was increased in SHR compared to WKY, but passive efflux of preaccumulated $Ca^{2+}$ from the vesicles was decreased in SHR. The data indicate that the membrane vesicles of rat mesenteric arteries exhibit $Na^+-Ca^{2+}$ exchange activity. It is also suggested that changes of this process in vascular smooth muscle cell membrane of SHR may be involved in higher intracellular $Ca^{2+}$ concentration and higher basal tone in SHR.

• 대한수의학회지
• /
• 제44권1호
• /
• pp.7-13
• /
• 2004

Severe hypertension (>180 mmHg) develops in spontaneously hypertensive rats (SHR) after 12 wk-old; however, it is not clear whether what kinds of molecular mechanism leads to altered cardiac performance following developmental stages in SHR. Also, although the effect of calcineurin (Cn) to promote cardiomyocyte hypertrophy in vivo and in vitro is established, its overall necessity as a hypertrophic mediator is currently an area of ongoing debate. Thus, we have examined i) body weight and blood pressure, ii) differences of expression and distribution of signaling molecules such as Cn, protein kinase B/Akt (PKB/Akt), and extracellular signal-regulated kinase (ERK) between SHR and their age-matched control Wistar-Kyoto (WKY) rats following developmental stages. In 16 wk-old SHR compared with WKY, 2-dimentional echocardiography showed cardiac enlargement and hypertrophy of left ventricle, significantly. Taken together, we suggest that Cn is associated with hereditary cardiac hypertrophy, the process being related to the molecular signaling mechanisms involving PKB/Akt and ERK.

• International Journal of Industrial Entomology and Biomaterials
• /
• 제14권2호
• /
• pp.121-126
• /
• 2007

Obesity is a major risk factor for cardiovascular disease. In our case study using animal models for disease states such as obesity or hypertension, we found that, Isaria sinclairii remarkably reduced body weight and ameliorated metabolic abnormalities in Zucker and SHR rats. Genetically obese (fa/fa) Zucker rats were one animal model chosen for this study. Four groups of rats received a standard diet and were treated orally with the following test samples daily for 8 weeks: saline (negative control), ethanol extracts of I. sinclairii, hot water extract of I. sinclairii, or $Xenical^{(R)}$ (30 mg/kg, positive control). Mild reductions (6.3%) in body weight gain were observed in the groups treated with the hot water extract of I. sinclairii compared to the control after 8 weeks. Interestingly, organ weight was greatly reduced by this Dongchunghacho (I. sinclairii), in parallel with the mild reductions in body weight gain and reductions in abdominal fat (adipose tissue). Also observed was a 4.1 % decrease in the ratio of heart weight/body weight compared to the control group. As a hypertensive animal model, SHR (spontaneously hypertensive rat) and WKY (Wistar Kyoto) rats were also administered these extracts for one month. Treatment with the hot water extract of I. sinclairii caused greater reductions in body weight gain for the SHR group (10.9%) compared to the WKY group's (5.2%). Based on these results, I. sinclairii extracts contain selective action for anti-obesity activity, naturally occurring candidate for regulation of body weight increase, as demonstrated in the present study.

• 생약학회지
• /
• 제30권2호
• /
• pp.226-230
• /
• 1999

We have isolated a sesquiterpene lactone, cumambrin A from the dried flowers of Chrysanthemum boreale Makino and reported its chemical structure. The aim of the present study was to investigate whether the exogenous administration of cumambrin A has a pharmacological effect on normalization of blood pressure in the spontaneously hypertensive rats (SHR). In vitro studies: Relaxative response induced by cumainbrin A was increased with dose-dependent manner and showed maximizing response at a concentration of $5{\times}10^{-4}M$. Further, this relaxative response was significantly increased at a condition of endothelium present than that of endothelium denuded. In vivo studies: The normalizing effect of cumambrin A on blood pressure was also increased with time-dependent manner and then gradually recovered to normal condition at approximately 4 hrs after cumambrin A treatment.

• Archives of Pharmacal Research
• /
• 제11권4호
• /
• pp.301-307
• /
• 1988

Relationship between the maintenance of hypertension and central serotonergic nervous system activity in opontaneously hypertensive rats (SHR) was studied. Serotonin turnover-rates were measured in 5 brain areas as an index of serotonergic neuronal activity and compared at the ages of 14 weeks in two types of animals; (1) spontaneously hypertensive rats (SHR) (2) normotensive wistar kyoto rats (WKY). In 14-week old SHR, central serotonin turnover rate was significantly lower in telencephalon, hypothalamus/thalamus and midbrain than normotensive rat, but significantly higher in cerebellum. There were no significant differences between serotonin turnover rate in pons/medulla of SHR and that of normotensive rat. THese data suggest that the abnormally lower turnover rates of serotonin in telencephalon, hypothalamus/thalamus and midbrain may be one of the underlying neuronal factors for manifestation of hypertension in SHR.

• 한국한의학연구원논문집
• /
• 제12권3호통권18호
• /
• pp.59-67
• /
• 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.