• Korean Journal of Food Science and Technology
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• v.38 no.4
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• pp.567-570
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• 2006

This study was carried out to investigate the effect of antihypertensive peptides originating from marine proteins on ACE inhibitory activity and systolic blood pressure in spontaneously hypertensive rats (SHR). Sixteen male SHR (SHR/NCrj) weighing approximately 270 g were randomly divided into few experimental groups based on diet: C (control), A (anchovy), P (pollack) and M (mackerel). The final body weights of P and M groups were higher, than those of C and A groups, but difference was not significant. Average reference blood pressure (RBP) was 224 mmHg at 12 weeks old. Compared with RBP, final systolic blood pressure of the marine peptide oops after 28 days of feeding with anchovy, pollack and mackerel fractions by gavage was decreased by 9.0% (A), 10.2% (P) and 14.3% (M), respectively, but was not different in C. Especially, final blood pressure of M was lower by 32 mmHg than RBP. These results suggested that peptide originated from mackerel hydrolysate was considered to have an antihypertensive fraction as effective lowering of blood pressure in SHR.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.2
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• pp.174-179
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• 2007

This study was carried out to investigate the effect of Gastrodiae elata Blume fractions on systolic blood pressure and serum lipid profiles in spontaneously hypertensive rats (SHR/NCrj) fed high fat diet. Twenty-four males SHR weighing approximately 160 g were randomly divided into four groups; A (low molecule, GR-1), B (polysaccharide, GR-2), C (protein, GR-3) fractions of G. elata Blume, respectively, and D (high fat diet as control). After orally tube feeding the fractions of G. elata Blume, there were no differences in final body weights among the treatment groups. Diet intake was somewhat high in the control group (D), but there were no significant differences in feed efficiency ratios. In terms of serum lipid profiles, total-cholesterol level was statistically higher in the control group (D) than in G. elata Blume fraction groups (p<0.05). Triglyceride levels of low molecule (A) and polysaccharide (B) groups were lower by 16% and 11%, respectively than that of the control group (D). HDL-cholesterol level was remarkably higher (p<0.05), whereas LDL-cholesterol level was significantly lower (by 25%) in the group B as compared to the control group (D). Atherogenic index (AI) of G. elata Blume fraction groups were significantly lower than in the control group (p<0.05). Reference blood pressure (RBP) showed an average of $180\sim190mmHg$ at 8 weeks old after 3 weeks on feeding high fat diet. Compared with RBP, final blood pressure of treatment groups (35 days after feeding the fractions of G. elata Blume gractions) were decreased by 1.7% (A), 5.5% (B) and 3.6% (C), respectively, but the control group (D) contrarily showed an increase of 2.6%. Especially, final systolic blood pressure of the polysaccharide group (B) was lower by 22 mmHg than that of the control group (D). From these findings, it can be suggested that polysaccharide fraction may improve blood serum lipids and should be considered as effective in lowering of blood pressure.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.3
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• pp.464-468
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• 2003

The antihypertensive and cholesterol- lowering effects of Monascus koji (M. koji) prepared with Monascus ruber IFO32318 were examined in spontaneously hypertensive rats (SHR). Control was fed a normal diet and groups I, II or III were fed diets containing 0.03%, 0.1% or 0.3% M. koji for 8 weeks, respectively. After 8 weeks, all animals were fed normal diets in the following 2 weeks. The blood pressure of rats fed M. koji added diets were significantly attenuated as compared with control and the diet containing high concentration of M. koji had a tendency of stronger antihypertensive effect. These differences lasted throughout the experimental period when they were fed experimental diet. For 2 weeks after the 8 weeks of experimental diet all groups were fed the same normal diet and the differences of blood pressure caused by M. koji disappeared. In rats fed the M. koji added diet, the serum total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C) were not differed compared with control, but VLDL cholesterol (VLDL-C) was significantly lowered. M koji also significantly decreased serum risk factors, both TC/HDL-C ratio and non HDL-C/HDL-C ratio. Consequently, it is suggested that M. koji may play an important role to attenuate hypertension and to improve serum lipid Profiles.

• Journal of Pharmaceutical Investigation
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• v.20 no.4
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• pp.223-228
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• 1990

The contribution of endogenous transport systems to the blood-brain barrier (BBB) transport of basic and acidic drugs was studied by using a carotid injection technique in rats and an isolated bovine cerebrovascular disease state were compared between the normotensive rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) which have been well established as an animal model with pathogenic similarities to humans. Basic drugs such as eperisone, thiamine and scopolamine inhibited, in a concentration dependent manner the in vivo uptake of $[{^3}H]choline$ through BBB, whereas amino acids and acidic drugs such as salicylic acid and valproic acid did not inhibit the uptake. The uptake of $[^3H]choline$ by B-CAP increased with time and showed a remarkable temperature dependency. The uptake of $[^3H]choline$ by B-CAP showed the very similar inhibitory effects as observed in the in vivo brain uptake, and was competitively inhibited by a basic drug, eperisone. The in vivo BBB uptakes of $[^3H]acetic$ acid and $[^{14}C]salicylic$ acid were dependent on pH of the injectate and the concentration of drugs. Several acidic drugs such such as salicylic acid, benzoic acid and valproic acid inhibited the in vivo uptake of $[^3H]acetic$ acid, whereas amino acid, choline and a basic drug such as eperisone did not inhibit the uptake. The uptake of acetic acid by B-CAP was competitively inhibited by salicylic acid. The permeability surface area product (PS) through BBB for $[^3H]choline$ in SHRSP was significantly lower than that in WKY. The concentration of choline in the brain dialysate in SHRSP was about half of that in WKY, while no significant difference was observed in the plasma concentration of choline between SHRSP and WKY. No significant difference was observed in the transport of monocarboxylic acids, glucose and neutral amino acid through BBB between SHRSP and WKY. From these results, it was concluded that BBB transport system of choline contributes to the transport of basic drugs through BBB, that acidic drugs can be transported via a moncarboxylic acid BBB transport system and that the specific dysfuntion of the BBB choline transport in SHRSP was ascribed to the reduction of the maximum velocity of choline concentration in the brain interstitial fluids.

• IMMUNE NETWORK
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• v.9 no.2
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• pp.64-73
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• 2009

Background: 15d-$PGJ_2$ has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-$PGJ_2$ on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. Methods: Effect and action mechanism of 15d-$PGJ_2$ on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-${\kappa}B$ avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity. Results: 15d-$PGJ_2$ decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-$PGJ_2$ in SHR VSMCs was mediated through PPAR${\gamma}$, and dependent on NF-${\kappa}B$ activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-$PGJ_2$ on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-$PGJ_2$ on LPS-induced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-$PGJ_2$/LPS. Conclusion: Our results indicate that the upregulatory effect of 15d-$PGJ_2$ on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPAR${\gamma}$ and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-$PGJ_2$/LPS-induced IL-8/CXCL8 expression in SHR VSMCs.

• YAKHAK HOEJI
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• v.41 no.6
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• pp.802-816
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• 1997

In order to investigate the pharmacological properties of New Woohwangehungsimwon Pill (NWCH). Effects of Woohwangehungsimwon Pill (WCH) and NWCH were compared using various experimental models. In isolated rat aorta, NWCH and WCH showed the relaxation of blood vessels in maximum contractile response to phenylephrine ($10^{-6}$M) without regard to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxative effects of NWCH and WCH. NWCH and WCH inhibited the vascular contractions induced by acethylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats(SHRs), NWCH and WCH decreased significantly heart rate. These, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, these had no effects on parameters of action potential at low doses, whereas inhibited the cardiac, contractility at high doses. Furthermore, these had a significant inhibitory effects on heart acceleration in normotensive rats and SHRs. These results suggested that NWCH and WCH have weak cardiovascular effects, and that there is no significant differences between two preparations.

• Journal of Ginseng Research
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• v.26 no.4
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• pp.178-186
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• 2002

The present study was attempted to investigate the effects of total ginseng saponin (G75), panaxadiol-type (PDS) and panaxatriol-type saponin (PTS) on contractile responses of vasoconstrictors in aortic smooth muscle stripes of normotensive (NR) and spontaneous hypertensive rats (SHR). Phenylephrine (an adrenergic $\alpha$$\_$1/-receptor agonist) and high potassium (a membrane depolarizing agent) caused greatly contractile responses in both NR and AHR aorta, respectively. Phenylephrine- and high potassium-induced contractile responses were greater in NA than those in SHR aortic smooth muscle stripes. In NR, the contractile responses of high potassium (5.6$\times$10$\^$-2/ M) were not affected in the presence of GTS (300 $\mu$g/ml), PDS (300 $\mu$g/ml), and PTS (300 $\mu$g/ml), respectively whereas phenylephrine (10$\^$-6/ M)-induced contractile responses were markedly inhibited. In SHR, the contractile responses of high potassium (5.6$\times$10$\^$-2/ M) were not affected in the presence of GTS (300 $\mu$g/ml), PDS (300 $\mu$g/ml), and moderate doses of PTS (150-300 $\mu$g/ml), respectively but greatly blocked by high concentration of PTS (600 $\mu$g/ml). Phenylephrine (10$\^$-6/ M)-induced contractile responses were inhibited in a dose dependent fashion (150-600 $\mu$g/ml) by the pretreatment with PTS while not altered in the presence of GTS (300 $\mu$g/ml) and PDS (300 $\mu$g/ml), respectively. Taken together, these experimental results suggest that ginseng saponins cause vascular relaxation through blockade of adrenergic $\alpha$$\_$1/-receptors and some unknown mechanisms, and that there is some difference in sensitivity of vascular smooth muscle between NR and SHR in responses to ginseng saponins. It seems that panaxatriol type of some ginseng saponins has the greatest potency in vascular relaxation.

• Korean Journal of Food Science and Technology
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• v.26 no.3
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• pp.213-220
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• 1994

Gastrodia (G) Rhizoma has been used clinically as an oriental herbal medicine with sedative, anticonvulsive, and depressor effects. The present study tested effects of G. Rhizoma extracts on the coronary circulation and myocardial oxygen consumption in perfused rat hearts. Sprague Dawley rats (SD) and spontaneously hypertensive rats (SHR) were employed as experimental animals and nonworking Langendorff heart perfusion technique introduced for heart experiments. G. Rhizoma extracts were prepared from grinding G. Rhizoma into powder, extracting in water and 50% ethanol for 4 or 16 hr and diluting with Krebs-Henseleit bicarbonate perfusion buffer to be 70%. Hearts were perfused with bicarbonate buffer oxygenated with 95% $O_{2}:$ 5% $CO_{2}$ at constant coronary perfusion pressure of $90cmH_{2}O$. The diluted extracts were infused into coronary arteries in a concentration of $1{\sim}5\;{\mu}M$ for $7{\sim}8 min. While in SD water- or ethanol-extracts of G. Rhizoma extracted for 16 hr increased coronary perfusate flow (CPF) and decreased coronary vascular resistance (CVR), ethanol-extracts in SHR produced coronary vasoconstriction associated with enhanced CVR. G. Rhizoma extracts-induced increase in CPF reduced myocardial oxygen extraction, and thus myocardial oxygen consumption ($MVO_{2}$) remained at that observed prior to infusion of extracts. In SD and SHR 16 hr-water-extracts markedly altered coronary venous effluent pH and $Pco_{2}$ and evoked metabolic acidosis, which could be a coronary vasodilator mechanism decreasing CVR. In this study, the extracts decreasing CVR in SD and SHR did not augment the lactate production. Therefore, although the effects of the extracts on cardiac function and coronary circulation depended on solvents and duration for extraction, the 16hr-water-extracts, at least, exhibited coronary vasodilation in SD and SHR. Conversely, ethanol-extracts constricted coronary arteries in SHR. G. Rhizoma extracts-induced vasodilation might be due to the metabolic acidosis rather than due to the increased lactate production. The results indicate that G. Rhizoma extracts obtained from proper extracting procedures can be used as a safe and clinically applicable herbal medicine in the cardiovascular diseases such as coronary artery disease and hypertension for vasodilatory and antihypertensive actions.

• Microbiology and Biotechnology Letters
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• v.39 no.2
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• pp.126-132
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• 2011

The goal of this study was to develop a high value Korean red wine possessing antihypertension activity. The effects of some medicinal plants and grapes on the alcohol fermentation process and the angiotensin I-converting enzyme (ACE) inhibitory activity of Vitis hybrid red wine were investigated. Various Vitis hybrid red wines were vinified by the fermentation of a mixture of Vitis hybrid must and some medicinal plants and grapes at $25^{\circ}C$ for 10 days. Of these red wines, the Vitis hybrid-Vitis coignetiae red wine exhibited a high ethanol content of 12.0% and had a good level of acceptability. It also showed a high antihypertensive ACE inhibitory activity of 68.5%. After post-fermentation of 60 days, the ACE inhibitory activities of the Vitis hybrid-Vitis coignetiae red wine exhibited the highest ACE inhibitory activity of 80.7% ($IC_{50}$: 28 mg/mL) and also had the best acceptability. The $C_{18}$ solid phase extracts of the Vitis hybrid-Vitis coignetiae red wine, after 60 days post-fermentation, showed clear antihypertensive effects on spontaneously hypertensive rats. Our results reveal that the Vitis hybrid-Vitis coignetiae red wine has the potential to become a new functional red wine due to its good acceptability and high antihypertensive activity.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.517-526
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• 2009

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC $(20\sim180\;{\mu}g/ml)$ perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC $(60\;{\mu}g/ml)$, the CA secretory responses to veratridine (a selective $Na^+$ channel activator $(10\;{\mu}M)$, Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, $10\;{\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, $10\;{\mu}M$) were significantly reduced, respectively. In the simultaneous presence of PCRC $(60\;{\mu}g/ml)$ and L-NAME (an inhibitor of NO synthase, $30\;{\mu}M$), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high $K^+$, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC $(60\;{\mu}g/ml)$ was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.