• The Korean Journal of Physiology
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• 제27권2호
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• pp.217-225
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• 1993

The role of endogenous brain angiotensin ll (Ang ll) in mediating the cardiovascular and vasopressin responses to hemorrhage was assessed in conscious spontaneously hypertensive rats (SHR), and normotensive Wistar-Kyoto (WKY) rats. Artificial cerebrospinal fluid (aCSF) with or without losartan (DuP 753), a specific Ang ll receptor subtype I $(AT_1)$ antagonist and saralasin, a combined $AT_1/AT_2$ antagonist was administered into the cerebral lateral ventricle. Hemorrhage was performed at a rate of 3 ml/kg/min far 5 min. Intracerebroventricular administration of losartan and saralasin had no effect on the basal blood pressure. However, in response to acute hemorrhage, central Ang ll antagonists produced a remarkably greater fall in blood pressure, a reduced tachycardia, and an enhanced renin release compared with the aCSF control experiment in SHR, but effected no significant change in WKY rats. Central Ang ll-blocked SHR showed significantly lower blood pressure and heart rate during the recovery period than the aCSF control rats. Vasopressin release tallowing the hemorrhage was attenuated by icv Ang ll antagonists: the effect was more pronounced in SHR than in WKY rats. Centrally administered losartan and saralasin produced remarkably similar effects on the cardiovascular function and vasopressin responses to hemorrhage. These data suggest that brain Ang ll acting primarily through AT, receptors plays an important physiological role in mediating rapid cardiovascular regulation and vasopressin release in response to hemorrhage especially in Hypertensive rats.

• 한국한의학연구원논문집
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• 제13권2호통권20호
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• pp.149-155
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• 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 and Pharmacology
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• 제22권6호
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• pp.713-719
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• 2018

Dipeptidyl peptidase4 (DPP4) inhibitors such as gemigliptin are antidiabetic drugs elevating plasma concentration of incretins such as GLP-1. In addition to the DPP4 inhibition, gemigliptin might directly improve the functions of vessels under pathological conditions. To test this hypothesis, we investigated whether the acetylcholine-induced endothelium dependent relaxation (ACh-EDR) of mesenteric arteries (MA) are altered by gemigliptin pretreatment in Spontaneous Hypertensive Rats (SHR) and in Wistar-Kyoto rats (WKY) under hyperglycemia-like conditions (HG; 2 hr incubation with 50 mM glucose). ACh-EDR of WKY was reduced by the HG condition, which was significantly recovered by $1{\mu}M$ gemigliptin while not by saxagliptin and sitagliptin up to $10{\mu}M$. The ACh-EDR of SHR MA was also improved by $1{\mu}M$ gemigliptin while similar recovery was observed with higher concentration ($10{\mu}M$) of saxagliptin and sitagliptin. The facilitation of ACh-EDR by gemigliptin in SHR was not observed under pretreatment with NOS inhibitor, L-NAME. In the endothelium-denuded MA of SHR, sodium nitroprusside induced dose-dependent relaxation was not affected by gemigliptin. The ACh-EDR in WKY was decreased by treatment with $30{\mu}M$ pyrogallol, a superoxide generator, which was not prevented by gemigliptin. Exendin-4, a GLP-1 analogue, could not enhance the ACh-EDR in SHR MA. The present results of ex vivo study suggest that gemigliptin enhances the NOS-mediated EDR of the HG-treated MA as well as the MA from SHR via GLP-1 receptor independent mechanism.

• Biomolecules & Therapeutics
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• 제16권4호
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• pp.343-350
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• 2008

Oroxylin A is a flavonoid isolated from Scutellaria baicalensis, which is one of the most important medicinal herbs in traditional Korean medicine. In this study, we investigated the psychopharmacological activities of oroxylin A using the open field, rota-rod, balanced wire and plus-maze tests in Spontaneously Hypertensive Rats (SHR) and Wistar Kyoto Rats (WKY). Oroxylin A reduced hyperactivity in SHR (ADHD animal model) although it tended to increase locomotor activity in WKY. Methylphenidate did not reduce hyperactivity. Oroxylin A alleviated impulsive behaviors such as rearing, the percentage of moving time to the central area and the tendency to move into an unstable condition (open area in elevated plus-maze). Methylphenidate also reduced the percentage of staying time in the central area and the tendency to move into an unstable condition. Both oroxylin A and methylphenidate enhanced motor attention in SHR and WKY. Oroxylin A antagonized the muscimol ($GABA_A$ receptor agonist)-induced $Cl^-$current and its action was similar to that of bicuculline ($GABA_A$ receptor antagonist). The effects of oroxylin A may be caused by the antagonism at the $GABA_A$ receptor. Thus, oroxylin A may be a candidate of drug for treatment of ADHD.

• 한국한의학연구원논문집
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• 제12권3호통권18호
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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.

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

• The Korean Journal of Physiology and Pharmacology
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• 제13권4호
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• pp.309-313
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• 2009

Spontaneous hypertensive rats (SHR) are an established model of genetic hypertension. Vascular smooth muscle cells (VSMC) from SHR proliferate faster than those of control rats (Wistar-Kyoto rats; WKY). We tested the hypothesis that induction of heme oxygenase (HO)-1 induced by aprotinin inhibits VSMC proliferation through cell cycle arrest in hypertensive rats. Aprotinin treatment inhibited VSMC proliferation in SHR more than in normotensive rats. These inhibitory effects were associated with cell cycle arrest in the G1 phase. Tin protoporphyrin IX (SnPPIX) reversed the anti-proliferative effect of aprotinin in VSMC from SHR. The level of cyclin D was higher in VSMC of SHR than those of WKY. Aprotinin treatment downregulated the cell cycle regulator, cyclin D, but upregulated the cyclin-dependent kinase inhibitor, p21, in VSMC of SHR. Aprotinin induced HO-1 in VSMC of SHR, but not in those of control rats. Furthermore, aprotinin-induced HO-1 inhibited VSMC proliferation of SHR. Consistently, VSMC proliferation in SHR was significantly inhibited by transfection with the HO-1 gene. These results indicate that induction of HO-1 by aprotinin inhibits VSMC proliferation through cell cycle arrest in hypertensive rats.

• 대한수의학회지
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• 제44권1호
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• pp.7-13
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• 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.

• 대한약리학회지
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• 제30권1호
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• pp.75-86
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• 1994

선천성 고혈압 흰쥐(SHR)와 정상혈압 흰쥐에서 교감신경성 신경전달에 미치는 부신수질 및 renin-angiotensin계의 역할을 알아보기 위해, 부신수질을 제거하거나 angiotensin 변환 효소 억제제를 장기간 처치한 뒤 중추신경계가 파괴된 상태에서 절전신경을 자극했을 때 나타나는 승압반응과 대동맥의 catecholamine농도 및 angiotensin 변환 효소 활성도의 변화를 비교 검토하였다. 부신수질을 제거하더라도 중추신경계를 파괴하기 전후의 혈압에는 영향을 주지 못했으며, 절전 신경 자극에 의한 승압반응은, 자극 주파수에 의존적으로 증가하였으며 prazosin 전처치로서 거의 완전히 억제되었다. 정상혈압 흰쥐에서와는 달리, 선천성 고혈압 흰쥐에서는 부신수질을 제거했을 때는 절전신경 자극에 의한 승압반응이 부신수질을 제거하지 않는 군(이하 대조군)에 비하여 유의하게 약화되었다. SHR에서 부신수질 제거로 부신 catecholamine 함량은 현저히 감소되었고, 혈청의 angiotensin 변환 효소 활성도는 감소되는 경향을 나타내었다. 그러나 혈장 및 대동맥 절편의 catecholamine 함량, 대동맥 절편의 angiotensin 변환 효소의 활성도는 대조군과 유의한 차이가 없었다. 그러나 WKY에서는 부신수질이 제거된 군에서 대동맥 절편의 angiotensin 변환 효소의 활성도와 catecholamine함량이 대조군에 비해 유의하게 증가되어 있었다. Enalapril처치에 의해서 선천성 고혈압 흰쥐 평균 혈압은, 부신 catecholamine 함량 및 대동맥 절편의 angiotensin 변화 효소의 활성도와 함께 현저히 저하되어 정상혈압 흰쥐와 유사하였다. 그리고 선천성 고혈압 흰쥐에서 부신수질의 제거로 절전신경 자극에 의한 승압반응이 대조군에 비하여 약화되는 현상은 enalapril을 처치하였을 때는 관찰되지 않았다. 이상의 결과로 미루어보아 교감신경성 신경전달을 항진시키는 부신수질의 작용은 renin-angiotensin계의 활성화에 의존적이었으며, 부신수질의 제거로 정상혈압 흰쥐에서는 renin-angiotensin계가 보상적인 조절이 일어났으나, 선천성 고혈압 흰쥐에서는 보상적인 조절이 일어나지 않았다.

• Nutrition Research and Practice
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• 제6권4호
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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.