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.
Na Young Cheul;Nam Gung Uk;Lee Yang Koo;Kim Dong Hee
Journal of Physiology & Pathology in Korean Medicine
/
v.18
no.1
/
pp.243-249
/
2004
KBPT is the fortified prescription of Bang-pung-tong-sung-san(BPTS) by adding Spatholobi Clulis and Salviae Miltiorrzae Radix. BPTS prescription has been utilized in oriental medicine for the treatments of vascular diseases including hypertension, stroke, and arteriosclerosis. Yet, the overall mechanism underlying its activity at the cellular levels remains unknown. Using spontaneously hypertensive rat (SHR) model, we investigated whether the KBPTS has an effect on the pathophysiological parameters related to hypertension. Pretreatment of SHR with KBPTS was found to lower blood pressure and heartbeat rate. Levels of aldosterone. dopamine, and epinephrine were found to be significantly reduced in the serum of KBPTS-treated SHR. Histological examination of adrenal cortex and superior aorta showed that tissues from KBPTS-treated SHR rats were more intact and cleaner compared to saline-treated control. Levels of superoxide dismutase (SOD) protein in adrenal gland, aorta, myocardial tissue, and kidneys were higher in KBPTS-treated animals than control group. The present data suggest that KBPTS may play a role in normalizing cardiovascular function in SHR by controlling hypertension-related blood factors and superoxide stressors.
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.
The age-related changes of monoamine contents and monoamine oxidase (MAO) activities in the whole brain and blood pressures were measured and compared every week during the ages of 5 weeks to 12 weeks in two types of animals; (1) spontaneously hypertensive rats (SHR) and (2) normotensive Sprague-Dawley rats (NR). Blood pressures in SHR began to rise at the ages of 7 or 8 weeks and were significantly higher thereafter than in NR. Abnormally low MAO activities in the brain of SHR were detected from the ages of 8 weeks. Comparisons were also made between brain monoamine-norepinephrine, dopamine and 5-hydroxytrytamine contents of SHR and those of NR at the same ages throughout the test period. In SHR, none of those monoamine values was consistently higher or lower than in NR during the test period. Protein contents of the brain between SHR and NR were not significantly different at any ages. These observations suggest that the abnormally low MAO activities in SHR brain may be one of the underlying neurological factors for the susceptibilities to hypertension and the deficit of MAO activities may be due to the changes in properties rather than in amount of this enzyme.
Background: Extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling by remodeling the 6-O-sulfation of heparan sulfate proteoglycans on the cell surface. The present study examined the effects of Sulfs on angiotensin II (Ang II)-induced hypertensive mediator expression and vascular smooth muscle cells (VSMCs) proliferation in spontaneously hypertensive rats (SHR). Methods: Ang II receptors, 12-lipoxygenase (12-LO), and endothelin-1 (ET-1) messenger RNA (mRNA) expressions in SHR VSMCs were analyzed by real-time polymerase chain reaction and Western blotting. VSMCs proliferation was determined by [$^3H$]-thymidine incorporation. Results: Basal Sulfs mRNAs expression and enzyme activity were elevated in SHR VSMCs. However, Sulfs had no effect on the basal or Ang II-induced 12-LO and ET-1 mRNA expression in SHR VSMCs. The inhibition of Ang II-induced 12-LO and ET-1 expression by blockade of the Ang II type 2 receptor ($AT_2\;R$) pathway was not observed in Sulf1 siRNA-transfected SHR VSMCs. However, Sulf2 did not affect the action of $AT_2\;R$ inhibitor on Ang II-induced 12-LO and ET-1 expression in SHR VSMCs. The down-regulation of Sulf1 induced a reduction of $AT_2\;R$ mRNA expression in SHR VSMCs. In addition, the inhibition of Ang II-induced VSMCs proliferation by blockade of the $AT_2\;R$ pathway was mediated by Sulf1 in SHR VSMCs. Conclusion: These findings suggest that extracellular sulfatase Sulf1 plays a modulatory role in the $AT_2\;R$ pathway that leads to an Ang II-induced hypertensive effects in SHR VSMCs.
The present study designed to investigate whether hwangryunhaedok-tang show an anti-hypertensive effect and elucidate its possible mechanism in spontaneously hypertensive rats. The systolic blood pressures (SBP) were significantly decreased as an oral administration of hwangryunhaedok-tang compared with their control group. The urine volume was significantly increased by administration of hwangryunhaedok-tang but urinary sodium (UNaV), potassium (UKV), chloride excretion (UCIV) were not remarkably affected. The urinary creatinine excretion rate (UcrV) was significantly increased in rats administered with hwangryunhaedok-tang in association with increase of creatinine clearance (Ccr). The urine osmolality (Uosmol) was significantly decreased in SHR administered with hwangryunhaedok-tang without being changed in solute-free water reabsorption ( TcH20). The expressions of Aquaporin 2 (AQP-2). 3 and ${\alpha}\;1$, ${\beta}\;1$ subunits of Na.K-ATPase were determined by Western blot analysis to assess the role of these proteins in association with changes of renal functions in SHR administered with hwangryunhaedok-tang. The expression of AQP-2 and 3 protein was significantly down-regulated in the kidney of SHR administered with hwangryunhaedok-tang compared with those in control rats without being altered expression of ${\alpha}\;1$, ${\beta}\;1$ subunits of Na,K-ATPase. In the in vitro assay, Angiotensin converting enzyme (ACE) was inhibited by hwangryunhaedok-tang in a dose-dependent manner. Berberine and/or palmatine, which are well known as a main components of hwangryunhaedok-tang, also have an ACE inhibitory effects in a dose-dependent manner. Taken together, these results suggest that hwangryunhaedok-tang lowered blood pressure through the increase of diuresis caused by down-regulation of water channels and the inhibition of Angiotensin converting enzyme.
The renoprotective effects of Korean Red Ginseng were examined in STZ-induced diabetic spontaneously hypertensive rats (SHR). After 3 day administration of streptozotocin (STZ), animals were divided into four groups : Group 1, hypertensive rats (H); Group 2, hypertensive rats with diabetes (HD); Group 3, hypertensive rats with diabetes administered with 100 mg/kg of ginseng total saponin(GTS); Group 4, hypertensive rats with diabetes administered with 600 mg/kg of ginseng non-saponin (GNS). After 2 weeks oral administraions of GTS and GNS, body weight, kidney weight, plasma glucose, urinary albumin excretion, serum creatinine, urea nitrogen and blood pressure were examined. After 3,7 and 21 day of STZ administration, expressions of TGF-${\beta}$1 and fibronectin in kidney were analyzed by immunoblotting and/or immunohistochemistry. GTS and GNS treatments slightly decreased blood pressure when compared to H and HD groups. Also, GTS and GNS treatments ameliorated kidney hypertrophy without affecting plasma glucose levels. Meanwhile, GNS treatment increased Cu/Zn-SOD activity in kidney and generally showed more efficient renoprotective effects than GTS. We suggest that the renoprotective effects of ginseng partially result from downregulations of TGF-${\beta}$1, fibronectin expressions and anti-oxidative activity of ginseng non-saponin.
To investigate the hypotensive effect of germinated brown rice, spontaneously hypertensive rats were randomly divided into 4 groups and fed with experimental diets for 6 weeks; control group fed with standard diet, rice group fed with diet containing 50% rice, brown rice group fed with diet containing 50% brown rice and germinated brown rice group fed with diet containing 50% germinated brown rice. Body weight gain and FER (food efficiency ratio) of germinated brown rice group, $86.3\;{\pm}\;11.1\;g$ and $10.4\;{\pm}\;1.4%$, were significantly lower than those of other groups. Systolic blood pressure of germinated brown rice group after feeding for 6 weeks was $169.2\;{\pm}\;6.2\;mmHg$, which was significantly lower than those of other groups and decreased largely compared to that of beginning stage. And blood triglyceride of germinated brown rice group, $138.4\;{\pm}\;29.5\;mg/dL$, was significantly lower than those of other groups, but all groups didn't s show significantly difference in total and HDL-cholesterol of blood. These results suggested that germ mated brown rice had hypotensive effect on spontaneously hypotensive rats.
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.
$Na^+-Ca^{2+}$ 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.
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