• Archives of Pharmacal Research
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• v.12 no.2
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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.

• 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.

• Korean Journal of Veterinary Research
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• v.41 no.4
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• pp.579-582
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• 2001

Twenty one Spontaneously Hypertensive Rats(SHR) that were 4- to 21-month-old were examined histopathologically and serologically during a routine health monitoring of the rat colony. The results of the enzyme linked immunosorbent assay(ELISA) for murine pathogens demonstrated that 14 of 21 SHR rats had antibodies to Mycoplasma pulmonis. Histopathologically, the mycoplasma positive SHR rats were observed to have the typical pulmonary lesions which are characterized by the hyperplasia of the lymphoid tissue around the bronchi, bronchioles and vessels. Based on the histopathological findings and serological results, this case was diagnosed as a murine mycoplasmosis of SHR rats.

• IMMUNE NETWORK
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• v.9 no.3
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• pp.106-113
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• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.359-364
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• 2002

The present study examined the effects of water extract of Hwangruynhaedoktang plus Yukmijihwangtang add Chogudeung (HYC) on the blood pressure and renal function in spontaneously hypertensive rats (SHR). The HYC water extract blocked increase of systolic blood pressure (SBP) in SHR. The urinary volume (UV), sodium (UNaV), potassium (UkV), and chloride (UclV) excretions were significantly increased in SHR administered with high dose of water extract of HYC, but urinary osmolality was not changed. The creatinine clearance (Ccr), which is index of glomerular filtration rate (GFR), was increased by administration of HYC, while solute-free water reabsorption (TcH2O) was not changed. Taken together, these results suggest that the depressor effects of HYC, at least in part, caused by diuretic effect due to increase of glomerular filtration rate.

• Proceedings of the Korean Biophysical Society Conference
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• 1999.06a
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• pp.53-53
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• 1999

We have investigated whether alterations in the expression levels of sarcoplasmic reticulum (SR) $Ca^{2＋}$ regulatory proteins in heart and mesenteric arteries from different models of hypertension would occur. Nephrectomied diabetic-hypertensive rats (DM-HT) and spontaneously hypertensive rats (SHR) were used as models of hypertension.(omitted)

• Korean Journal of Veterinary Research
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• v.57 no.3
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• pp.181-187
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• 2017

Antihypertensive effects of ethanol extracts of Aralia elata (Miq.) Seem. (AE) were investigated in spontaneously hypertensive rats (SHR). SHR aged 14 weeks were treated for 8 weeks with AE (10 or 50 mg/kg/day) or amlodipine besylate (Am; 10 mg/kg/day) orally. Hypertension results in injury to several organs and can produce a significant increase in malondialdehyde (MDA) content as a result of lipid peroxidation and endothelial dysfunction. In this study, oral administration of AE and Am significantly reduced systolic blood pressure, organ weight index, and MDA content in tissues but increased significantly the plasma nitrite and nitrate concentrations. The endothelium-dependent relaxant activities of acetylcholine ($10^{-10}-10^{-3}M$) in norepinephrine (NE)-precontracted aorta were increased in AE- and Am-treated rats. Particularly strong endothelium-dependent relaxant activities were observed in AE-treated (50 mg/kg) rats. The endothelium-independent relaxant activities of sodium nitroprusside ($10^{-10}-10^{-3}M$) in NE-precontracted aorta were not changed. The results of this study suggest that AE has both antihypertensive and end-organ protective effects in SHR.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.216-216
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• 1996

The purpose of the present study was to determine whether in vivo noradrenergic neural activity in the locus coeruleus is related to the development of hypertension. Two groups of animals were prepared, 1) young spontaneously hypertensive rats (SHR) and 2) age-matched normotensive wistar kyoto rats (WKY). At il weeks of age, the release of norepinephrine (NE) and 3,4-dihydroxyphenylglycol (DOPEG) from locus coeruleus of young SHR and WKY as an index of neural activity were determined by in vivo microdialysis along with blood pressure (BP) at three conditions : 1) normal; 2) elevated BP by systemic injection of phenylephrine and 3) alpha-1 adrenoceptor stimulated by perfusion of phenylephrine into the locus coeruleus through microdialysis probe. Basal releases of NE and DOPEG from the iocus coeruleus were 0.415+/-0.089pg/20min, 1.311+/-0.293 pg/20min in SHR and 0.204+/-0.078 pg/20min, 1.492+/-0.365 pg/20min in WKY respectively. Basal release of NE from the locus coeruleus of SHR was significantly greater than that of WKY. Phenylephrine systemic injection caused elevation of BP in both SHR and WKY in a dose related manner. Following phenyephrine injection, the releases of NE and DOPEG from the locus coeruleus of SHR were significantly decreased, whereas there were no significant changes in the releases of NE and DOPEG In young WKY. Alpha-1 adrenoceptor stimulation in the locus coeruleus by perfused phenylephrine through microdialysis probe caused pressor responses in both SHR and WKY, but the magnitude of pressor response in SHR was larger compared with that in WKY. The result from the present study suggests that noradrenergic neural activity in locus coeruleus may contribute as one of triggering factors for the expression of hypertension in young SHR.

• The Korean Journal of Physiology
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• v.28 no.2
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• pp.181-190
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• 1994

Endothelium-derived relaxing factor (EDRF) activates guanylate cyclase which mediates the formation of cGMP from GTP in vascular smooth muscle. It is well known that endothelium-dependent relaxation is impaired in spontaneously hypertensive rats (SHR). However, it is still unknown whether the impaired endothelium-dependent relaxation in SHR results from the reduced release of EDRF or from the decrease of vascular response to EDRF. We investigated the effects of cGMP on the contractility and Ca movement in the aorta of SHR and Wistar-Kyoto rats (WKY). The amplitude of the endothelium-dependent relaxation to actylcholine (ACh) was significantly less in SHR than in WKY. L-arginine $(10^{-3}M)$ did not increase endothelium-dependent relaxation in both strains. Sodium nitroprusside (SNP), an activator of guanylate cyclase, relaxed the 40 mM $K^+-induced$ contraction in a dose-dependent manner $(10^{-10}{\sim}10^{-6}\;M)$ in the endothelium-rubbed aortic strips of both strains. However, there was no significant difference in these relaxations between WKY and SHR. 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP), a cell membrane-permeable derivative of cGMP relaxed the 40 mM $K^+-induced$ contraction in a dose-dependent manner $(10^{-6}{\sim}10^{-4}\;M)$ in the endothelium-rubbed aortic strips of both strains. Also norepinephrine $(10^{-6}\;M)-induced$ contractions in normal and Ca-free Tyrode's solution were suppressed by the pretreatment with 8-Br-cGMP $(10^{-4}\;M)$ in either strain. However, the amplitudes of suppression induced by 8-Br-cGMP were greater in SHR than that in WKY. Basal $^{45}Ca$ uptake and 40mM $K^+-stimulated\;^{45}Ca$ uptake were not suppressed by pretreatment with 8-Br-cGMP $(10^{-4}\;M)$ in single aortic smooth muscle cells of both SHR and WKY. From the above results, it is suggested that cGMP decreases Ca sensitivity in vascular smooth muscle cells and that the impaired endothelium-dependent relaxation in the aortic strips of SHR is not the result of a reduced vascular response to EDRF.

• Food Science of Animal Resources
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• v.30 no.4
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• pp.545-550
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• 2010

The effects of casein hydrolysate on blood pressure (BP) and serum lipid profiles were investigated in spontaneously hypertensive rats (SHR). Twenty-four 6-wk old male SHRs were assigned to 3 groups in a completely randomized design. Experimental groups were as follow: control, market milk group (MLG) and casein hydrolysate group (CHG). Reference blood pressure (RBP) showed average $198.94{\pm}1.46mmHg$. Blood pressure (BP) of CHG reduced 24 mmHg after 2 wk of treatment, but these increased after 3 wk. BP of CHG was significantly lower than BP of Control in experimental time (p<0.05). Serum lipid profiles were not differ significantly among groups (p<0.05). These data suggest that casein hydrolysate may beneficially improvement of blood pressure level in SHR.