• IMMUNE NETWORK
• /
• 제9권3호
• /
• pp.106-113
• /
• 2009

Background: We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC. Methods: Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 ($AT_1$) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [$^3H$]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings. Results: Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the $AT_1$ receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an $AT_1$ receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor. Conclusion: These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.

• 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.

• Environmental Analysis Health and Toxicology
• /
• 제7권1_2호
• /
• pp.59-65
• /
• 1992

The role of central dopaminergic neural activity for the maintenance of hypertension was tested. Two groups of animals were prepared; 1) Spontaneously hypertensive rats (SHR) at 14 weeks of age which reveal hypertension and 2) age-matched normotensive Wistar Kyoto rats (WKY). Blood pressures and dopamine turnover rate were measured from animals in each group. Dopamine turnover rate was determined in four brain regions such as telence-phalon, hypothalamus/thalamus, midbrain and pons/medulla, from concentration of dopamine at time zero, 1 and 2 hours after alpha-methyl-para-tyrosine (AMPT) was injected into animals. In SHR dopamine turnover rate was greater than normotensive rats in only midbrain. The result from the present study implicates that dopaminergic neural activity in midbrain may be positively coupled to the manifestation of hypertension in SHR.

• 약학회지
• /
• 제59권4호
• /
• pp.184-189
• /
• 2015

We compared impulsive behaviors in Wistar rats and in Wistar-Kyoto rats. There was no significant difference in locomotor activity between them. However, Wistar rats showed high activity in 5-choice serial reaction time track. When Wistar rats were treated with atomoxetin (3 mg/kg), methylphenidate (2 mg/kg) or amphetamine (2 mg/kg), they showed less impulsive behavior. Serotonin contents in prefrontal cortex and brain stem also increased. In conclusion, we suggest that Wistar rats could be used as animal model for impulsive behavior analysis. In addition, serotonin might be related with this impulsivity.

• 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.

• Journal of Pharmaceutical Investigation
• /
• 제23권1호
• /
• pp.1-9
• /
• 1993

The endothelial cell of brain capillary called the blood-brain barrier (BBB) has carrier-mediated transport systems for nutrients and drugs. The mechanism of the BBB transport of basic and acidic drugs has been reviewed and examined for endogenous transport systems in BBB in WKY and SHRSP. Acidic drugs such as salicylic acid and basic drugs such as eperisone are taken up in a carrier mediated manner through the BBB via the monocarboxylic acid and amine transport systems. The specific dysfunction for the choline transport at the BBB in SHRSP would affect the function of the brain endothelial cell and brain parenchymal cell. The utilization of the endogenous transport systems of monocarboxylic acid and amine could be promising strategy for the effective drug delivery to the brain.

• 한국식품영양과학회지
• /
• 제44권4호
• /
• pp.483-490
• /
• 2015

본 연구는 본태성 고혈압 쥐인 SHR을 이용하여 복분자 완숙과 에탄올 50% 추출물의 혈압 강하 효과 및 그와 관련된 인자들[endothelial nitric oxide synthase(eNOS), homocysteine, plasminogen activator inhibitor-1(PAI-1), albumin, creatinine, blood lipid 등]에 미치는 영향을 조사하였다. 본태성 고혈압 쥐에게 복분자 완숙과 에탄올 50% 추출물을 12주간 투여한 결과 수축기 혈압이 고혈압대조군에 비하여 약 12% 억제되었다. 또한 eNOS 유전자 발현을 유의하게 증가하였으며 혈청 homocysteine 및 PAI-1의 활성이 눈에 띄게 감소됨을 확인하였다. 또한 심근 호산성 세포수를 감소시켜 심장의 손상 및 병변을 경감시키는 효과가 있음을 확인하였다. 그러나 혈중 지질 및 혈청 albumin, creatinine의 농도에는 각 군 간의 변화가 뚜렷하게 나타나지 않았다. 본 연구 결과 복분자 완숙과 에탄올 50% 추출물은 혈관의 손상을 야기할 수 있는 homocysteine이나 PAI-1과 같은 염증성 인자로부터 혈관을 보호하고 이를 통해 eNOS의 유전자 발현을 개선시킴으로써 혈압의 조절에 영향을 미치는 것으로 나타났으며, 향후 심혈관계 질환의 개선에 도움이 되는 식품소재로서의 가능성이 있음을 확인하였다.

• IMMUNE NETWORK
• /
• 제9권2호
• /
• pp.64-73
• /
• 2009

Background: 15d-$PGJ_2$ has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-$PGJ_2$ on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. Methods: Effect and action mechanism of 15d-$PGJ_2$ on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-${\kappa}B$ avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity. Results: 15d-$PGJ_2$ decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-$PGJ_2$ in SHR VSMCs was mediated through PPAR${\gamma}$, and dependent on NF-${\kappa}B$ activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-$PGJ_2$ on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-$PGJ_2$ on LPS-induced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-$PGJ_2$/LPS. Conclusion: Our results indicate that the upregulatory effect of 15d-$PGJ_2$ on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPAR${\gamma}$ and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-$PGJ_2$/LPS-induced IL-8/CXCL8 expression in SHR VSMCs.

• 한국식품과학회지
• /
• 제46권3호
• /
• pp.375-383
• /
• 2014

본 연구는 복분자 완숙과 50% 에탄올 추출물을 이용하여 인간제대정맥내피세포주(HUVEC)에서 복분자 추출물이 NO의 생성에 미치는 영향과 ACE 단백질 발현을 조사하였으며, 본태성 고혈압 흰쥐(SHR)에서 혈압강하 효과 및 혈압의 조절과 관련 깊은 인자들(renin, AT1-R, ET-1, IL-6)의 유전자 발현 그리고 혈관조직의 변화를 조사하였다. 그 결과 복분자 완숙과 50% 에탄올 추출물은 HUVEC 세포주에서 NO의 생성을 촉진하였으며 혈관수축활성을 가지는 ACE 단백질의 발현을 억제하였고 본태성 고혈압 흰쥐에게 복분자 완숙과 에탄올 50% 추출물을 8주간 투여한 결과 혈액 내 ACE의 활성이 억제되었으며 renin 및 혈관 수축인자인 ET-1 유전자의 발현이 억제되고 염증관련 유전자인 IL-6의 발현이 억제됨을 확인하였다. 그리고 신세동맥의 두께 및 심근 호산성세포수를 감소시켜 혈관내피세포의 손상을 보호하며 심장의 병변을 경감시키는 효과가 있음을 확인하였다. 본 연구 결과 복분자 완숙과 추출물은 혈압 조절과 연관된 단백질 및 유전자의 발현과 활성을 조절하고, 혈관의 두께 및 심근의 변성을 감소시켜 혈압 강하에 도움이 되는 것으로 나타났으며 향후 심혈관계 질환을 개선시킬 수 있는 식품소재로서의 가능성이 있음을 확인하였다.