• The Korean Journal of Physiology
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• v.30 no.1
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• pp.21-31
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• 1996

To investigate the mechanisms of increased endothelium-dependent contraction by acetylcholine in hypertensive rats, the relationship between endothelium-dependent contraction by acetylcholine and blood pressure was studied in spontaneously hypertensive rats (SHR), one-kidney, one clip Goldblatt hypertension (1K,1C-GBH) rats, and Wistar-Kyoto rats (WKY). SHR were treated orally with enalapril or nicardipine in order to prevent development of hypertension or suppress the developed hypertension. 1K,1C-GBH rats were made by renal artery stenosis with contralateral nephrectomy in 8 week-WKY. 1. Endothelium-dependent contractions by acetylcholine $(10^{-6}{\sim}10^{-5}\;M)$ in SHR were significantly greater than those in WKY. 2. Chronic treatment with enalapril or nicardipine reduced the endothelium-dependent contraction in SHR 3. The degree of reduction of endothelium-dependent contraction was greater in SHR which was prevented from developing hypertension than in SHR of which high blood pressure was suppressed. 4. In aortic rings from 1K,1C-GBH rats, endothelium-dependent contractions by acetylcholine were augmented as compared with WKY. 5. There is good relationship between the value of blood pressure and magnitude of endothelium-dependent contraction. Thus, it is suggested that increased endothelium-dependent contraction in hypertensive rats may he due to the high blood pressure and endothelium-dependent contraction may not be a cause of the initiation of hypertension in SHR.

• Archives of Pharmacal Research
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• v.14 no.3
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• pp.242-248
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• 1991

Antihypertensive effect of YH 334 was examined in various experimental hypertension rat models and the systemic and regional hymohynamic profiles of the compound were investigated in conscious spontaneously hypertensive rats (SHR). The antiypertensive potensive potency of YH 334 is found to be more than 10 times stronger than that of nitrendipine in the all hypertensive models. The effective doses to lower the initial blood pressure by 20% $(ED_{20})$ of YH334 were 1.4 mg/kg in normotensive rats (NR), 0.7 mglkg in SHR. 0.1 mg/kg in DOCA salt hypertensive rats (DHR) and 0.4 mg/kg in renal hypertensive rats (RHR), and the $ED_{20}$ values of nitrendipine were 15.8 mg/kg in NR, 7.1 mg/kg in SHR, 1.7 mg/kg in DHR and 4.8 mg/kg in RHR. The primary hemodynamic effect hemodynamic profile is similar to that of nitrendipine. Both compounds seem to produce potent antihypertensive effects by lowering peripheral resistance in the skeletal muscles. In the organ bath study using isolated rabbit aorta, YH 334 was found to be a potent voltage dependent calcium channel blocker without significant inhibitory effect on the receptor operated calcium channels like the most of other dihydropyridine type calcium antagonists. Furthermore, YH334 showed acute diuretic and natriuretic effects in conscious SHR, which may render the unnecessary restriction of sodium in the diet of those patients on long term hypertension therapy. This effect would provide an additional benefit to its potent antihypertensive activity.

• Nutrition Research and Practice
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• v.17 no.2
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• pp.192-205
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• 2023

BACKGROUND/OBJECTIVES: It is known that the renin-angiotensin system (RAS) in the brain could regulate cognitive functions as well as blood pressure. Inhibition of RAS for the improvement of cognitive function may be a new strategy, but studies so far have mostly reported on the effects of RAS inhibition by drugs, and there is no research on cognitive improvement through RAS inhibition of food ingredients. Therefore, this study investigated the effect of curcumin on blood pressure and cognitive function and its related mechanism in spontaneously hypertensive rat/Izm (SHR/Izm). MATERIALS/METHODS: Six-week-old SHR/Izm rats were divided into 5 groups: control group (CON), scopolamine group (SCO, drug for inducing cognitive deficits), positive control (SCO and tacrine [TAC]), curcumin 100 group (CUR100, SCO + Cur 100 mg/kg), and curcumin 200 group (CUR200, SCO + Cur 200 mg/kg). Changes in blood pressure, RAS, cholinergic system, and cognitive function were compared before and after cognitive impairment. RESULTS: The SCO group showed increased blood pressure and significantly reduced cognitive function based on the y-maze and passive avoidance test. Curcumin treatments significantly improved blood pressure and cognitive function compared with the SCO group. In both the CUR100 and CUR200 groups, the mRNA expressions of angiotensin-converting enzyme (ACE) and angiotensin II receptor type1 (AT1), as well as the concentrations of angiotensin II (Ang II) in brain tissue were significantly decreased. The mRNA expression of the muscarinic acetylcholine receptors (mAChRs) and acetylcholine (ACh) content was significantly increased, compared with the SCO group. CONCLUSIONS: The administration of curcumin improved blood pressure and cognitive function in SCO-induced hypertensive mice, indicating that the cholinergic system was improved by suppressing RAS and AT1 receptor expression and increasing the mAChR expression.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.98-98
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• 2001

It has been suggested that hyperuricemia is related to the development of essential hypertension. Hypertensive patients with hyperuricemia has decreased glomerular filtration activity as compared to normotensive patients with hyperuricemia. These studies indicates uric acid concentrations in blood is associated with hypertension, Probenecid is an uricosuric agent which decreases uric acid reabsorption at the proximal tubule. Recently, we have shown that probenecid exerts anti-hypertensive action in Spontaneously Hypertensive Rats. Considering these results, I have designed a series of experiments to explore potential mechanism of antihypertensive action, of probenecid. In isolated rat thoracic aorta. probenecid significantly prevented phenylephrine-induced contraction of the blood vessel. When endothelium removed blood vessels were used, probenecid produced same effect as the intact blood vessels, indicating that probenecid directly act through the ${\alpha}$ -adrenergic receptor in vascular smooth muscles rather than through endothelium. These results suggest that one of the mechanism of antihypertensive effects of probenecid is due to the direct inhibition of ${\alpha}$ -adrenergic receptor in blood vessels.

• 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 and Pharmacology
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• v.20 no.6
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• pp.621-628
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• 2016

Hypertension can be caused by various factors while the predominant causes include increase in body fluid volume and resistance in the circulatory system that elevate the blood pressure. Consumption of probiotics has been proven to attenuate hypertension; however, the effect is much strain-dependent. In this study, a newly isolated Lactobacillus casei (Lb. casei ) strain C1 was investigated for its antihypertensive properties in spontaneously hypertensive rats (SHR). Lactic acid bacteria (LAB) suspension of 11 log colony-forming unit (CFU) was given to SHR (SHR+LAB, n=8), and phosphate buffer saline (PBS) was given as a control in SHR (SHR, n=8) and in Wistar rats as sham (WIS, n=8). The treatment was given via oral gavage for 8 weeks. The results showed that the weekly systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and aortic reactivity function were remarkably improved after 8 weeks of bacterial administration in SHR+LAB. These effects were mostly attributed by restoration of wall tension and tensile stress following the bacterial treatment. Although not statistically significant, the level of malondialdehye (MDA) in SHR+LAB serum was found declining. Increased levels of glutathione (GSH) and nitric oxide (NO) in SHR+LAB serum suggested that the bacterium exerted vascular protection through antioxidative functions and relatively high NO level that induced vasodilation. Collectively, Lb. casei strain C1 is a promising alternative for hypertension improvement.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.119-124
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• 1997

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.

• The Korean Journal of Food And Nutrition
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• v.33 no.5
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• pp.493-504
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• 2020

Gastrodia elata Bl. (GE) is a traditional herbal medicine used for the treatment hypertension and cerebrovascular disease. The purpose of this study was to investigate the antioxidant effect and blood pressure control ability of the GABA containing fermented Gastrodia elata Blume. The fermentation strain provided by Dr. Gi in Seoul National University is L. brevis GABA100, excellent strain of GABA production, which is involved in the ability to degrade gastrodin glycosides and activation of brain function. The Gastrodia elata Blume fermented by Lactobacillus brevis GABA 100 showed antioxidant activity (total phenolic contents, DPPH radical and ABTS anion scavenging activities) than unfermented Gastrodia elata Blume. In the spontaneously hypertensive rats (SHR), the concentration of fermented Gastrodia elata Blume was administered at 500, 1,000, and 2,000 mg/kg for 8 weeks. Systolic blood pressure decreased statistically significantly (p<0.05), especially 2 weeks after feeding fermented Gastrodia elata Blume. Also, it showed a significant decrease in low, medium, and high concentrations of fermented Gastrodia elata Blume at 4 weeks and 8 weeks. These results indicated that Gastrodia elata Blume fermented by the excellent strain of GABA production L. brevis GABA100 shows the antioxidant function and the effect of suppressing the increase in blood pressure.

• Biomolecules & Therapeutics
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• v.16 no.4
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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.

• Journal of Ginseng Research
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• v.38 no.4
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• pp.244-250
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• 2014

Background: Panax ginseng has distinct and impressive health benefits, such as improved blood pressure and immune system functioning. Rg3-enriched Korean Red Ginseng (REKRG) isolated from Korean Red Ginseng contains a high percentage of Rg3. Methods: In this study, we examined the effects of REKRG on endothelial cell nitric oxide synthase (eNOS) activation and adhesion molecules in endothelial cells and vascular function in rats. Results: REKRG dose-dependently increased eNOS phosphorylation and nitric oxide (NO) production in endothelial cells. In addition, REKRG markedly inhibited the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-mediated induction of intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expressions in endothelial cells. REKRG improved endothelium-dependent vasorelaxation in the Wistar-Kyoto (WKY) rat and spontaneously hypertensive rats (SHRs) compared with controls. Furthermore, REKRG treatment for 6 weeks increased serum NO levels and reduced the mean aortic intima-media thickness compared with controls. Conclusion: Taken together, these results suggest that REKRG increased vascular function and improved immune system functioning. Therefore, REKRG is a very useful food for preventing or improving various cardiovascular diseases.