This study was conducted to investigate the hypotensive effect of egg white protein (EWP) hydrolysate (EWH) in spontaneously hypertensive rats (SHRs). The hydrolysis of EWP was effectively performed with a combination of 0.5% bromelain and 1% papain at 50℃ for 60 min. The resulting hydrolysate did not elicit an allergic reaction as confirmed by human mast cell activation test. The systolic and diastolic blood pressures of the SHRs fed the EWH diet were observed to be significantly or numerically lower than those of the other groups during the experimental period of 28 d. EWH treatment significantly (p<0.05) upregulated the nitric oxide levels in hCMEC/D3 cells and the plasma of the SHRs compared to those in the control. Moreover, EWH ingestion significantly (p<0.01) reduced the plasma angiotensin II level of the SHRs compared with that in the control. In conclusion, beyond its basic nutritional value, EWH prevents and manages hypertension, and thus can be an invaluable resource for functional food development.
Radish (Raphanus sativus L.) is a cruciferous vegetable, and its leaves have antioxidant and anticancer properties. This study was conducted to evaluate the effects of ethyl acetate extracts from radish leaves on hypertension in 11-week-old spontaneously hypertensive rats (SHRs). The SHRs were randomly divided into 3 groups of 6 rats each on the basis of initial systolic blood pressure (SBP) and were treated with oral administration of radish leaf extract (0, 30, or 90 mg/kg body weight [bw], respectively) for 5 weeks. Six Wistar rats were used as normotensive controls. The amount of the radish leaf extract had no effect on body weight. The SBP of the SHRs showed a decreasing trend with the consumption of the radish leaf extract. In the third week, the SBP of the group fed 90 mg extract/kg bw reduced from 214 mmHg to 166 mmHg and was significantly lower than that of the normotensive and hypertensive controls. The extract did not show a significant effect on the angiotensin-converting enzyme (ACE) activity in the serum, kidney, and lung. The extract increased the concentration of NO in serum and the activities of antioxidant enzymes such as glutathione peroxidase and catalase in red blood cells (RBCs). The serum concentrations of $Na^+$ and $K^+$ were not significantly different between all groups. However, the fecal concentrations of $Na^+$ and $K^+$ increased; the fecal concentrations of $Na^+$ and$K^+$for the normotensive and hypertensive controls were not different. Urinary excretion of $Na^+$ was higher in the normotensive Wistar rats than in the SHRs, while that of $K^+$ was not significantly different. These findings indicate that consumption of radish leaves might have had antihypertensive effects in SHRs by increasing the serum concentration of NO and fecal concentration of $Na^+$ and enhancing antioxidant activities.
The purpose of the present study was to investigate whether polyphenol-rich fraction extracted from fruit wine of Rubus coreanum M (PCRC) can affect the contractility of the thoacic aortic strips isolated from spontaneously hypertensive rats (SHRs), and to clarify its mechanism of action. PCRC (200-800 ${\mu}g/mL$) concentration-depenedently blocked phenylephrine (10 ${\mu}M$)-induced contractile responses of the isolated aortic strips of SHRs. PCRC (400 ${\mu}g/mL$), added in to bath medium, also depressed the contractile active tension evoked by both phenylephrine (3 and 10 ${\mu}M$) and high potassium (25 and 56 mM). In the simultaneous presence of PCRC (400 ${\mu}g/mL$) and L-NAME (a selective inhibitor of NO synthase, 300 ${\mu}M$), the contractile responses evoked by phenylephrine and high $K^+$ were recovered to considerable level of the corresponding control contractility compared with those effects of PCRC-treatment alone. However, in the simultaneous presence of indomethacin (10 ${\mu}M$, a selective cyclooxygenase inhibitor) and PCRC (400 ${\mu}g/mL$), they were not affected. In the endothelium-denuded aortic strips by CHAPS-treatment, PCRC did not affect the contractile responses induced by phenylephrine or high potassium. Interestingly, PCRC (1.0, 3.0 and 10.0 mg/kg/30 min, i.v., respectively) dose-dependently suppressed norepiphrine-induced vasopressor responses in anesthetized SHRs. Collectively, we concluded that PCRC causes vasorelaxation in the thoracic aortic strips with intact endothelium of SHRs at least partly by the increased NO production through the activation of NO synthase of vascular endothelium, but not through the activation of cyclooxygenase. These results suggest that PCRC might be helpful to prevent or alleviate cardiovascular diseases, including hypertension.
Background: Korean Red Ginseng (Panax ginseng) has been shown to exert antihypertensive effects. In particular, ginsenoside Rg3 is thought to be a potent modulator of vascular function. The present study was performed to examine the antihypertensive efficacy of Korean Red Ginseng (KRG) extract and Rg3-enriched KRG (REKRG) extract. Methods: Spontaneously hypertensive rats (SHRs) andWistar-Kyoto rats (WKYs) were divided into six groups (WKY control, WKY-KRG, WKY-REKRG, SHR control, SHR-KRG, and SHRREKRG), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at the carotid artery, followed by injection of 3mg/kg KRG or 3mg/kg REKRG. Results: REKRG treatment significantly decreased SBP and DBP 3hours post-treatment in the SHR group compared with SHR control group. However, SBP and DBP were not significantly different in KRG-treated SHRs compared with control SHRs. REKRG treatment did not significantly alter SBP or DBP 3hours post-treatment in the WKY group compared with WKY control group. Similarly, there were no differences in SBP or DBP with KRG treatment in the WKY group and WKY control group. Both KRG and REKRG increased endothelial nitric oxide synthase phosphorylation levels in the aorta, and the increases in endothelial nitric oxide synthase phosphorylation levels by REKRG treatment were higher than those with KRG treatment. Similarly, nitric oxide production in plasma from WKYs and SHRs was also increased by both KRG and REKRG. Conclusion: These results suggest that REKRG has a more beneficial effect on blood pressure control than KRG in SHRs.
Journal of the Korean Society of Food Science and Nutrition
/
v.18
no.1
/
pp.1-13
/
1989
The present study was designed to examine the effect of dietary fish oil on blood pressure and lipid status of serum. Weanling SHRs and normotensive Wistars were fed a diet containing 5%(w/w) mackerel oil(MO), soybean oil(SO) or beef tallow(BT) for 8 weeks. Growth rate was not significantly different among three dietary groups, but that of SHRs was silightly lower than that of Wistars. SHRs showed higher systolic blood pressure than Wistar rats from the beginning and become hypertensive (over 150mmHg) after 6 week s of feeding period. The MO group of SHRs showed the lowest blood pressure at the 8th week of feeding period but that of Wistars showed similar values with other groups. Tissue weights of liver, heart and kidney were not different amongdietary aroups in Wistars and SHRs. However, heart and kidney weights of SHRs were significantly higher than those of Wistars. Microscopic examination revealed that endomysium of heart tissue and urinary space of kidney were narrowed in SHRs. Serum total and HDL-cholesterol showed similar values among three different dietary fat groups but triglyceride levels were significantly low in MO groups. HDL-cholesterol levels of SHRs were lower than those of Wistars, as well as the fractions of total HDL, the sum of HDL and $HDL_{2+3}$, while VLDL fractions were higher in SHRs. MO groups had the lower values of $HDL_1,\;HDL_{2+3}$ratio than SO and BT groups. Major dietary fatty acids were more or less incorporated into serum phospholipid and triglyceride, resulting in the characteristic fatty acid profile of each dietary group. Incorporation of $C_{18:2}({\omega}_6)$ in SO groups were pronounced, but the degree of incorporation was lower in SHRs. In Mo groups, $C_{22:6}({\omega}_3)$ levels were inreased in triglyceride. It is suggested that these changes in serum lipid fatty acid composition are related to the different patterns of serum lipid by alteration of dietary fats.
The aim of the present study was to investigate the effect of Hwangryeonheadock-Tang and Onchung-Eum on essential hypertension and hyperlipidemia. Rats were orally administered for 30days with Hwangryeonheadock-Tang and Onchung-Eum and the blood was withdrawn at 10, 20 and 30days after an oral administration. The heart rate, tail blood pressure, plasma renin activity, plasma level of aldosterone. catecholamine, sodium and angiotensin II were measured after an oral administration of Hwangryeonheadock-Tang and Onchung-Eum in spontaneously hypertensive rat(SHR). In addition, serum levels of total cholesterol, triglyceride, HDL-cholesterol. LDL-cholesterol and total lipid were measured cholesterol-fed rats. The results were summarized as follows ; 1. A significant decrease of tail blood pressure was shown at 10, 20 and 30days after Hwangryeonheadock-Tang and Onchung-Eum treatment in SHRs. compared with saline. 2. Heart rate was significantly decreased at 30days in SHRs after Hwangryeonheadock-Tang treatment and at 20, 30days after Onchung-Eum treatment in SHRs. compared with the effects of saline group. 3, A significant decrease of plasma aldosterone level was elicited at 10, 20days after Hwangryeonheadock-Tang treatment in SHRs, compared with the effects of saline group, 4. Plasma renin activity was significantly decreased at 10days after Onchung-Eum treatment compared with the effects of saline group in SHRs. 5. Plasma norepinephrine level was significantly decreased at 20 and 30clays after Onchung-Eum treatment in SHRs, compared with the effects of saline group. 6. A significant decrease of plasma epinephrine level was induced at 30days after Hwangryeonheadock-Tang treatment and at 10, 20 and 30days after Onchung-Eum treatment, compared with the effects of saline group in SHRs. 7. Plasma sodium level was. significantly decreased at 20days after Hwangryeonheadock-Tang and Onchung-Eum treatment, compared with the effects of saline group in SHRs. 8. Plasma angiotensin II level was significantly decreased at 30days after Onchung-Eum treatment, compared with the effects of saline group in SHRs. 9. A significant decrease of body weight was observed at 20 and 30days after Hwangryeonheadock-Tang treatment and at 10, 20 and 30days after Onchung-Eum treatment. compared with the effects of saline group in hyperlipidemia rats. 10. Hwangryeonheadock-Tang and Onchung-Eum showed a significantly decreasing effect at 30days on serum total cholesterol level in hyperlipidemia rats, compared with the saline treatment. 11. Hwangryeonheadock-Tang and Onchung-Eum saw 20 and 30days respectively on serum triglyceride level in the saline treatment. 12. Hwangryeonheadock-Tang and Onchung-Eum decreased on serum HDL-cholesterol level significantly, compared with the saline treatment in hyperlipidemia rats. 13. A significant decrease of serum LDL-cholesterol was observed at 10 and 30days after Hwangryeonheadock-Tang treatment and at 30days after Onchung-Eum treatment, compared with the effects of saline group in hyperlipidemia rats. 14. Hwangryeonheadock-Tang had a significantly decreasing effect at 10, 20 and 30days on serum total lipid level, compared with the saline treatment in hyperlipidemia rats. 15. Hwangryeonheadock-Tang elicited a significantly decreasing effect on weight of kidneys, spleen and testes respectively and Onchung-Eum induced on weight of liver and spleen respectively in hyperlipidemia rats, compared with saline treatment. These Findings suggest a possible anti-hypertensive and anti-hyperlipidemic effect of Hwangryeonheadock-Tang and Onchung-Eum.
Chronic hypertension is associated with impaired endothelial function such as reduced synthesis/release of endothelium-derived relaxing factor(EDRF, nitric oxide) and increased synthesis/release of endothelium-derived contracting factor(EDCF) including prostaglandin endoperoxide($PGH_2$) , superoxide anion both in animals and in humans. We have previously shown that ginsenosides lower the blood pressure and enhance the release of nitric oxide(NO) from endothelial cells in the rat aorta of the normotensive rats. The aim of the present study is to examine whether in vivo treatment of spontaneously hypertensive rats(SHRs) with protopanaxatriol ginsenosides(PPT) reduces the blood pressure and improves endothelial function in the isolated thoracic aorta of SHR. In addition, the contractile response to $PGH_2$ and superoxide anion in the aorta treated with PPT was assessed. SHRs at the age of 16 weeks were savaged with PPT(30 mg/kg/ day) for 2 weeks and systolic blood pressure was measured by the tail-cuff method. Whereas blood pressure was significantly increased in SHRs by 5.4 mmHg during this period of treatment, treatment of SHRs with PPT blocked the elevation of blood pressure. Endothelium-dependent relaxation to acetylcholine was significantly increased in the PPT-treated animals. $PGH_2$- and oxygen-derived free radical-induced contractions were significantly suppressed in aortic rings without endothelium from PPT-treated SHR. These findings indicate that PPT reduces the blood pressure of SHR, which may be associated with either increase of NO release or by antagonizing superoxide anion and PGH2 in the aortic smooth muscle.
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.
Yang Yang;Shan Huang;Jun Wang;Xiao Nie;Ling Huang;Tianfa Li
The Korean Journal of Physiology and Pharmacology
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v.28
no.1
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pp.39-48
/
2024
Wogonin, extracted from the roots of Scutellaria baicalensis Georgi, has been shown to suppress collagen deposition in spontaneously hypertensive rats (SHRs). This study was performed to investigate the role and mechanism of wogonin underlying vascular remodeling in SHRs. After injection of SHRs with 40 mg/kg of wogonin, blood pressure in rats was measured once a week. Masson's trichrome staining was conducted to observe the changes in aortas and mesenteric arteries. Vascular smooth muscle cells (VSMCs) isolated from rat thoracic aortas were treated with Angiotensin II (Ang II; 100 nM) in the presence or absence of varying concentrations of wogonin. The viability and proliferation of VSMCs were examined using Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine assay, respectively. The migration of VSMCs was examined using wound healing assay and transwell assay. We found that wogonin administration alleviated hypertension, increased lumen diameter, and reduced the thickness of the arterial media in SHRs. Ang II treatment enhanced the viability of VSMCs, which was inhibited by wogonin in a concentration-dependent manner. Wogonin reversed Ang II-induced increases in the viability, proliferation, and migration of VSMCs. Moreover, wogonin inhibited Ang II-induced activation of mitogen-activated protein kinase (MAPK) signaling in VSMCs. Overall, wogonin repressed the proliferative and migratory capacity of VSMCs by regulating the MAPK signaling pathway, thereby attenuating vascular remodeling in hypertensive rats, indicating that wogonin might be a therapeutic agent for the treatment of vascular diseases.
Pharmacological effects of lemakalim on cardiovascular system were investigated using isolated rat hearts and conscious SHRs subjected to hyperkalemic and hypokalemic condition. In the isolated hearts perfused with normal physiological salt solution(4.7 mM KCI), lemakalim increased cardiac function and coronary flow, and these effects were significantly potentiated under hypokalemic(1.2, 2.5 mM KCI), but attenuated under hyperkalemic(IO mM KCI) condition. In conscious SHRS, lemakalim(0.1, 0.2, 0.3mg/kg, p.o.) produced a dose-related decrease in systolic blood pressure, the maximal hypotensive effect being reached around 0.5 hr after dosing. The intensity and the duration of hypotensive effect of lemakalim were significantly increased when administered in combination with dihydrochlorothiazide (2 mg/kg, p.o.), but decreased with triamterene(32 mg/kg, p.o.). It appears that the differential effects of two types of diuretics on the hypotensive action of lemakalim are due to their hypokalemic and hyperkalemic action, respectively. It is conclued that the concomitant use of $K^{+}$ channel openers and hypokalemic diuretics may be an appropriate model of combination therapy in the treatment of hypertension.
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