• Natural Product Sciences
• /
• 제13권1호
• /
• pp.68-77
• /
• 2007

The aim of the present study was to examine the effects of green tea extract (CUMS6335) on the release of CA evoked by cholinergic stimulation and direct membrane-depolarization in the perfused model of the adrenal gland isolated from the spontaneously hypertensive rats (SHRs), and to establish the mechanism of action. Furthermore, it was also to test whether there is species difference between animals, and between CUMS6335 and EGCG, one of biologically the most powerful catechin compounds found in green tea. CUMS6335 $(100\;{\mu}g/ml)$, when perfused into an adrenal vein for 60 min, time-dependently inhibited the CA secretory responses evoked by ACh (5.32mM), high $K^+$(56 mM), DMPP $(100\;{\mu}M)$, and McN-A-343 $(100\;{\mu}M)$ from the isolated perfused adrenal glands of SHRs. However, CUMS6335 itself did fail to affect basal catecholamine output. Also, in adrenal glands loaded with CUMS6335 $(100\;{\mu}g/ml)$, the CA secretory responses evoked by Bay-K-8644 $(10\;{\mu}M)$ and cyclopiazonic acid $(10\;{\mu}M)$ were also inhibited in a relatively time-dependent fashion. However, in the Presence of EGCG $(8.0\;{\mu}g/ml)$ for 60 min, the CA secretory response evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were not affected except for last period. Collectively, these results indicate that CUMS6335 inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by direct membrane-depolarization from the perfused adrenal gland of the SHR. It seems that this inhibitory effect of CUMS6335 is exerted by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of $Ca^{2+}$ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself. It seems likely that there is much difference in mode of the CA-releasing action between CUMS6335 and EGCG.

• Clinical and Experimental Pediatrics
• /
• 제62권3호
• /
• pp.95-101
• /
• 2019

Purpose: Increased apoptosis was recently found in the hypertrophied left ventricle of spontaneously hypertensive rats (SHRs). Although the available evidence suggests that apoptosis can be induced in cardiac cells by various insults including pressure overload, cardiac apoptosis appears to result from an exaggerated local production of angiotensin in adult SHRs. Altered expressions of Bcl associated X (Bax), Bcl-2, chemokine receptor (CCR)-2, monocyte chemoattractant protein (MCP)-1, transforming growth factor $(TGF)-{\beta}1$, phosphorylated extracellular signal-regulated kinases (PERK), and connexin 43 proteins, and kallikrein mRNA were investigated to explore the effects of losartan on the SHR model. Methods: Twelve-week-old male rats were grouped as follows: control (C), SHR (hypertension: H), and losartan (L; SHRs were treated with losartan [10 mg/kg/day] for 5 weeks). Western blot and reverse transcription polymerase chain reaction assays were performed. Results: Expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, PERK, and connexin 43 proteins, and kallikrein mRNA was significantly increased in the H group compared to that in the C group at weeks 3 and 5. Expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, and connexin 43 proteins and kallikrein mRNA was significantly decreased after losartan treatment at week 5. PERK protein expression was significantly decreased after losartan treatment at weeks 3 and 5. Bcl-2 protein expression was significantly decreased in the H group compared to that in the C group at weeks 3 and 5. Conclusion: Losartan treatment reduced expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, PERK, and connexin 43 proteins, and kallikrein mRNA in SHRs, along with decreased inflammation and apoptosis.

• 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.

• 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.

• 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.

• 한국식품과학회지
• /
• 제34권4호
• /
• pp.737-740
• /
• 2002

홍국의 혈압강화효능과의 관련성이 시사된 GABA 및 균체량 그리고 홍국이 나타내는 가장 큰 특성 중의 하나인 색도가 서로 다른 각 홍국추출물을 SHR에 경구투여하고 투여 1시간 후부터의 7시간 후까지 혈압강하효과에 미치는 영향을 측정하였다. 모든 홍국 투여군에서 혈압강하효과가 나타났으며 이 효과는 GABA나 균체량 또는 색도와 상관관계를 나타내지 않았다.

• Biomolecules & Therapeutics
• /
• 제5권3호
• /
• pp.299-305
• /
• 1997

In order to investigate the pharmacological properties of ι-muscone, effects of ι-muscone and musk were studied on the cardiovascular system with various experimental models. In isolated rat aorta, ι-muscone and musk made the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) in endothelium-containing rings of the rat aorta, but not in endothelium-denuded rings. However, ι-muscone and musk in the presence of the inhibitor of NO synthase and guanylate cyclase did not make the relaxation of blood vessels. In spontaneously hypertensive rats (SHRs), ι-muscone and musk slightly reduced blood pressure but significantly decreased heart rate. In the isolated perfused rat hearts, ι-muscone and musk did not affect significantly on LVDP, contractile force, coronary flow and (-dp/dt)/(+dp/dt). These results suggest that ι-muscone and musk have weak cardiovascular effects with relaxation of blood vessel and decrease of heart rate, but without significant cardiac functions.

• The Korean Journal of Physiology
• /
• 제22권2호
• /
• pp.295-305
• /
• 1988

It has been well known that the renal cortical blood flow rate was much higher than that of the medulla and the renal blood flow distribution was affected by hemorrhage, volume expansion or salt-loading. The existance of the heterogeneities of glomerular filtration rate and nephron has also been reported. In order to understand the regulations and physiological roles of the heterogeneities, studies on the intrarenal renin-angiotensin system have been focused. Although it is well known that the granularity of iuxtaglomerular cells and renal renin content are more marked in superficial than in the deep glomeruli, their physiological significance is not quite clear. This study was therefore undertaken to clarify changes in renin response and isoelectric ronin profile to TMB-8 in outer, mid and inner cotices of normotensive and hypertensive rats. The basal rate of renin release was highest in outer cortex of Sprague-Dawley rat (SDR), Wistar rat (WR) and spontaneously hypertensive rat (SHR). The basal renin release from outer and inner cortex of SHR was significantly lower than that from those of SDR. The reponse of renin release to TM8-8 was highest in mid cortex and the increase of renin release in response to TMB-8 from inner cortex of SDR was significantly higher than that in SHR. In dehydrated rats, the basal renin release from renal cortical slices of SDR was increased but that from WR and SHR was not. The response of renin release to TMB-8 from mid and inner cortex of dehydrated WR tended to increase. In dehyrated SHR, increase of renin release from inner cortex was significantly higher than that in euhydrated SHR. No significant differences in the isoelectric renin profile were found both in different cortical areas and strains. In dehydrated rats, the percentage of renin form 2 was decreased and those of renin form 5 and 6 were increased. These results suggest that the heterogeneity of renin release from cortical area of euhydrated and dehydrated rats in response to TMB-8 may be related to the changes of renal blood flow and/or calcium metabolism in cortical area. These data also suggest that the renin forms with different isoelectric points may have an physiological significance.

• Childhood Kidney Diseases
• /
• 제3권1호
• /
• pp.20-26
• /
• 1999

목 적 : 스트레스 유발 고혈압을 일으키는데 말초성 benzodiazepine수용체가 중요한 역할을 하리라 추정되어 왔다. 반복적 부동화 스트레스에 의한 신장의 말초성 benzodiazepine수용체의 변화 양상을 Sprague-Dawley rats와 boderline hypertensive rats의 두 실험동물군에서 비교, 관찰하여 고혈압을 유발하는데 신장의 말초성 benzodiazepine 수용체의 병태생리학적 기능을 규명하고자 하였다. Benzodiazepine수용체의 변화 양상은 방사성 동위원소를 사용한 수용체 결합 반응으로 검색하였으며 elevated plus maze검사로 각 실험동물의 불안도를 측정하여 각 군간의 결과를 비교, 관찰하였다. 방 법 : 불안도를 보기 위하여 측정한 plus-maze performance에서 percent open crosses는 Sprague-Dawley rats ($34.7{\pm}2.2$)에 비해 boderline hypertensive rats ($16.2{\pm}1.7$)가 유의하게 낮았고(P<0.05), percent time in open도 Sprague-Dawley rats ($22.5{\pm}1.0$)에 비해 boderline hypertensive rats ($12.1{\pm}1.2$)가 유의하게 낮아 불안도가 높은 상태임을 나타내었다(P<0.05). 스트레스를 주지 않은 Sprague-Dawley rats의 신장 말초성 benzodiazepine수용체의 수(Bmax: $5.5{\pm}0.6$pmol/mg protein)에 비하여 boderline hypertensive rats의 수용체의 수($3.1{\pm}0.7$pmol/mg protein)는 유의하게 낮았다(P<0.05). 하루 2시간씩 14일간 부동화 스트레스를 부하하였을 때, Sprague-Dawley rats와 boderline hypertensive rats에서 신장의 말초성 benzodiazepine 수용체의 수($7.4{\pm}0.7$ 및 $5.9{\pm}1.2$ pmol/mg protein)는 스트레스를 주지 않았을 때보다 증가하였으며(P<0.05), 스트레스에 노출된 boderline hypertensive rats는 스트레스에 노출된 Sprague-Dawley rats에 비하여 신장 말초성 benzodiazepine수용체의 수가 여전히 낮은 수준임을 관찰할 수 있었다(P<0.05). 결 론 : 이상의 결과로부터 신장의 말초성 benzodiazepine수용체는 스트레스 조절작용을 매개하며, 본 수용체의 수적 감소는 스트레스에 의한 고혈압 발생에 중요한 역할을 할 것으로 생각되었다.