• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.339-344
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• 2011

Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree widespread in northeast Asia. It is traditionally used for anticancer and anti-inflammatory therapy. The present study investigated the effect of an ethanol extract of UD on vascular tension and its underlying mechanism in rats. The dried root bark of UD was ground and extracted with 80% ethanol. The prepared UD extract was used in further analysis. The effect of UD on the cell viability, vasoreactivity and hemodynamics were investigated using propidium iodide staining in cultured cells, isometric tension recording and blood pressure analysis, respectively. Low dose of UD ($10{\sim}100{\mu}g/ml)$ did not affect endothelial cell viability, but high dose of UD reduced cell viability. UD induced vasorelaxation in the range of $0.1{\sim}10{\mu}g/ml$ with an $ED_{50}$ value of $2{\mu}g/ml$. UD-induced vasorelaxation was completely abolished by removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited calcium influx induced by phenylephrine and high $K^+$ and also completely abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100 mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner. Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in anesthetized rats. However, UD-induced hypotensive actions were minimized in L-NAME-treated rats. Taken together, out results showed that UD induced vasorelaxation and has antihypertensive properties, which may be due the activation of nitric oxide synthase in endothelium.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.4
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• pp.375-382
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• 1999

Growing evidence indicates that enhanced generation or actions of nitric oxide (NO) are implicated in the pathogenesis of hypertension in spontaneously hypertensive rats and diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. We investigated whether inducible nitric oxide synthase (iNOS) expression in STZ-induced diabetic rats is responsible for the alterations of vascular reactivity. Diabetic state was confirmed 28 days after injection of STZ (i.p) in rats by measuring blood glucose. In order to evaluate whether short term (4 weeks) diabetic state is related with altered vascular reactivity caused by iNOS expression, isometric tension experiments were performed. In addition, plasma nitrite/nitrate (NOx) levels and expression of iNOS in the lung and aorta of control and STZ-treated rats were compared by using Griess reagent and Western analysis, respectively. Results indicated that STZ-treated rats increased the maximal contractile response of the aorta to phenylephrine (PE), and high $K^+,$ while the sensitivity remained unaltered. Endothelium-dependent relaxation, but not SNP-mediated relaxation, was reduced in STZ-treated rats. Plasma nitrite/nitrates are significantly increased in STZ-treated rats compared to controls. The malondialdehyde (MDA) contents of liver, serum, and aorta of diabetic rats were also significantly increased. Furthermore, nitrotyrosine, a specific foot print of peroxynitrite, was significantly increased in endothelial cells and smooth muscle layers in STZ-induced diabetic aorta. Taken together, the present findings indicate that enhanced release of NO by iNOS along with increased lipid peroxidation in diabetic conditions may be responsible, at least in part, for the augmented contractility, possibly through the modification of endothelial integrity or ecNOS activity of endothelium in STZ-diabetic rat aorta.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.533-538
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• 2016

Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis.

• BMB Reports
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• v.52 no.2
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• pp.145-150
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• 2019

Endothelial dysfunction-induced lipid retention is an early feature of atherosclerotic lesion formation. Apoptosis of vascular smooth muscle cells (VSMCs) is one of the major modulating factors of atherogenesis, which accelerates atherosclerosis progression by causing plaque destabilization and rupture. However, the mechanism underlying VSMC apoptosis mediated by endothelial dysfunction in relation to atherosclerosis remains elusive. In this study, we reveal differential expression of several genes related to lipid retention and apoptosis, in conjunction with atherosclerosis, by utilizing a genetic mouse model of endothelial nitric oxide synthase (eNOS) deficiency manifesting endothelial dysfunction. Moreover, eNOS deficiency led to the enhanced susceptibility against pro-apoptotic insult in VSMCs. In particular, the expression of aggrecan, a major proteoglycan, was elevated in aortic tissue of eNOS deficient mice compared to wild type mice, and administration of aggrecan induced apoptosis in VSMCs. This suggests that eNOS deficiency may elevate aggrecan expression, which promotes apoptosis in VSMC, thereby contributing to atherosclerosis progression. These results may facilitate the development of novel approaches for improving the diagnosis or treatment of atherosclerosis.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.182-198
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• 2005

Object : This study was designed to research whether the protection and inhibitory effects of cardiovascular diseases in L-NAME induced rat or ECV 304 cell lines through the Cell morphological pattern, Tunel assay, LDH activity, heart rate, blood pressure and immunohistochemistric analysis by Boonsimgieum water extract Methods : Nitric oxide(NO) play an important role in normal and pathophysiological cells including as a messenger molecule, neurotransmitter, microbiocidal agent, or dilator of blood vessels and artheriosclerosis, hypertension, myocardial infarction, respectively. Endothelial cell products can modulate the magnitude of a response to a vasoconstrictor, as evinced by the greater constriction after endothelium removal or NO synthesis blockade. To investigate that Boonsimgieum in the potential contribution of the levels of nitric oxide generated by endothelial nitric oxide synthase (eNOS) and the mechanisms of protection against NG-nitro-L-arginine methyl ester (L-NAME), human ECV 304 cells, which normally do not express eNOS, were expressed by L-NAME. L-NAME stimulated rat or cells were found to be resistant to injury and delayed death following the Boonsimgieum. Inhibition of nitric oxide synthesis abolished the protective effect against L-NAME, thrombin and collagen exposure. Interestingly, such effects have been observed during stimulation with agents such as phenylephrine and KCl on L-NAME mediate rats, were damaged by the NOS inhibitor L-NAME. Result : As the result of this study, In group, the anti-apoptosis and necrosis in the cardiovascular system have a potential capacity for prevented, protected and treating the diseases of cardiovascular system, against the necrosis of rat and ECV 304 cells with Caspase 3 and calpain expression by L-NAME is promoted. Conclusion : these results demonstrate neuroprotective and memory enhancing effects of ZIBU, suggesting its beneficial actions for the treatment of AD.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.72-77
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• 2002

The present study was examined the effects of Bojungchiseup-tang water extract on the renal expression of renal function regulatory proteins including aquaporin 2 (AQP 2), aquaporin 3 (AQP 3), Na, K-ATPase α1 subunit, endothelial nitric oxide synthase (ecNOS), and inducible nitric oxide synthase (iNOS) in rats. The renal expression of AQP 3 was attenuated in rats administered with Bojungchiseup-tang water extract without altered expression of AQP 2, while ecNOS was up-regualted. Oral administration of Bojungchiseup-tang water extract (40 ㎕/100 g) also attenuated the renal expression of Na, K-ATPase α1-subunit and iNOS protein. These results suggest that the diuretic and natriuretic effects of Bojungchiseup-tang maybe causely related with a decreased expression of AQP 3 and increased expression of ecNOS.

• Preventive Nutrition and Food Science
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• v.18 no.1
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• pp.38-44
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• 2013

The protective effect of Polyopes lancifolia extract on high glucose-induced oxidative stress was investigated using human umbilical vein endothelial cells (HUVECs). High concentration of glucose (30 mM) treatment induced HUVECs cell death, but Polyopes lancifolia extract, at concentrations of 25, 50, and $100{\mu}g/mL$, protected cells from high glucose-induced damage. Furthermore, thiobarbituric acid reactive substances, intracellular reactive oxygen species, and nitric oxide levels increased by high glucose treatment were effectively decreased by treatment with Polyopes lancifolia extract in a dose-dependent manner. Also, Polyopes lancifolia extract treatment reduced the overexpressions of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor-kappa B proteins activation that was induced by high glucose in HUVECs. These results indicate that Polyopes lancifolia extract is a potential therapeutic material that will reduce the damage caused by high glucose-induced-oxidative stress associated with diabetes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2199-2202
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• 2015

The aim of the present study was to determine whether endothelial nitric oxide synthase (eNOS) gene polymorphisms play a role in development of bladder cancer in the Turkish population. The study was performed on 75 patients (64 men, 11 women) with bladder cancer and 143 healthy individuals (107 men, 36 women) with any kind of cancer history. Three eNOS gene polymorphisms (T-786C promoter region, G894T and intron 4 VNTR 4a/b) were determined with polymerase chain reaction and restriction fragment lenght polymorphism methods. In our study, GT and TT genotypes for eNOS G894T polymorphism were found to significantly vary among patients with bladder cancer and control group (OR: 0.185, CI: 0.078-0.439, p=0.0001 and OR: 0.324, CI: 0.106-0.990, p=0.026). Also, the frequency of the 894T allele was significantly higher in patients with bladder cancer (51%). No association was identified for eNOS T-786C and intron 4 VNTR 4a/b polymorphisms between patients with bladder cancer and control groups in our Turkish population.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.345-356
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• 2019

Docosahexaenoic acid (DHA), an omega-3-fatty acid, modulates multiple cellular functions. In this study, we addressed the effects of DHA on human umbilical vein endothelial cell calcium transient and endothelial nitric oxide synthase (eNOS) phosphorylation under control and adenosine triphosphate (ATP, $100{\mu}M$) stimulated conditions. Cells were treated for 48 h with DHA concentrations from 3 to $50{\mu}M$. Calcium transient was measured using the fluorescent dye Fura-2-AM and eNOS phosphorylation was addressed by western blot. DHA dose-dependently reduced the ATP stimulated $Ca^{2+}$-transient. This effect was preserved in the presence of BAPTA (10 and $20{\mu}M$) which chelated the intracellular calcium, but eliminated after withdrawal of extracellular calcium, application of 2-aminoethoxy-diphenylborane ($75{\mu}M$) to inhibit store-operated calcium channel or thapsigargin ($2{\mu}M$) to delete calcium store. In addition, DHA ($12{\mu}M$) increased ser1177/thr495 phosphorylation of eNOS under baseline conditions but had no significant effect on this ratio under conditions of ATP stimulation. In conclusion, DHA dose-dependently inhibited the ATP-induced calcium transient, probably via store-operated calcium channels. Furthermore, DHA changed eNOS phosphorylation suggesting activation of the enzyme. Hence, DHA may shift the regulation of eNOS away from a $Ca^{2+}$ activated mode to a preferentially controlled phosphorylation mode.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.379-383
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• 2000

Pathophysiological implications of the vascular nitric oxide (NO)/cGMP pathway in hypertension were investigated. Sprague-Dawley rats were made deoxycorticosterone acetate (DOCA)-salt hypertensive for six weeks. The protein expression of endothelial constitutive NO synthase (ecNOS) and the tissue content of NO were determined in the thoracic aorta. The protein expression and catalytic activity of soluble guanylyl cyclase (GC) were also determined. Systolic blood pressure measured on the day of experiment was significantly higher in the experimental group than in the control. The hypertension was associated with decreases in the vascular tissue content of NO metabolites, concomitantly with the expression of ecNOS proteins. The protein expression of GC was not affected, while its catalytic activity was significantly decreased in hypertension. These results indicate that the high blood pressure is associated with a decreased activity of vascular NO/cGMP pathway in DOCA-salt hypertension.