• Proceedings of the Korean Environmental Health Society Conference
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• 2005.06a
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• pp.303-305
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• 2005

3-Monochloro-1,2-propanediol (3-MCPD) is a contaminant of acid-hydrolyzed vegetable protein. Several reports have suggested that chronic exposure to 3-MCPD could produce neurotoxicity in vitro or neurobehavioral effects inaspects of experimental animals. Disturbance of the nitric oxide signaling pathway by chronic exposure to 3-MCPD may be a causal factor of neurological disorders in rats. In order to investigate the relationship between 3-MCPD administration and expression of inducibal nitric oxide synthase (iNOS), the numbers and distribution patterns of iNOS-immunoreactive neurons were examined. At the all three bregma level examined, the optical density of iNOS-postive neurons was significantly increased following exposure to 3-MCPD. The change was more severe in the upper layer than in deep layer of the cortex. These data suggest that 3-MCPD toxicity may be mediated through disturbances to the nitric oxide signaling pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.3
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• pp.263-270
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• 2000

To evaluate the involvement of nitric oxide production on the endothelium-dependent relaxation in diabetes, we have measured vascular and endothelial function and nitric oxide concentration, and the expression level of endothelial nitric oxide synthase in the streptozotocin-induced diabetic rats. Diabetic rats were induced by the injection of streptozotocin (50 mg/kg i.v.) in the Sprague-Dawley rats. Vasoconstrictor responses to norepinephrine (NE) showed that maximal contraction to norepinephrine $(10^{-5}\;M)$ was significantly enhanced in the aorta of diabetic rats. Endothelium-dependent relaxation induced by acetylcholine was markedly impaired in the aorta of diabetic rats, these responses were little improved by the pretreatment with indomethacin. However, endothelium-independent relaxation induced by nitroprusside was not altered in the diabetic rats. Plasma nitrite and nitrate $(NO_2/_3)$ levels in diabetic rats were significantly lower than in non-diabetic rats. Western blot analysis using a monoclonal antibody against endothelial cell nitric oxide synthase (eNOS) revealed that the protein level was lower in the aorta of diabetic rats than in non-diabetic rats. These data indicate that nitric oxide formation and eNOS expression is reduced in diabetes, and this would, in part, account for the impaired endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats.

• YAKHAK HOEJI
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• v.45 no.1
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• pp.116-124
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• 2001

Nitric oxide is a labile, gaseous, broad spectrum second messenger that used in various tissues and cells. If it is induced by endogenously and exogenously in the neuronal cells, it is able to mediate analgesia or hyperalgesia at the periphery and in the spinal level respectively. This dual role of nitric oxide in the sensory system is very intriguing but has not been fully understood yet. In this experiment, acetylcholine (300 $\mu$g/paw), sodium nitroprusside (600 $\mu$g/paw), and L-arginine (300 $\mu$g/paw) represented antinociceptive effect to noxious topical stimulus, but pronociceptive responses followed by spinally application (20$\mu$g/5$\mu$l, 10$\mu$g/3$\mu$l, 500$\mu$g/5$\mu$l respectively). Calcium ion is critical element which activates nitric oxide synthase, therefore verapamil (300 $\mu$g/paw) and NOS inhibitor (20 mg/kg, L-NAME or L-NOArg) are injected into right hind paw (i.pl.). When verapamil is combined with NOS inhibitors analgesic effects through NO-cGMP pathway are inhibited as compared with ACh alone. Diluted formalin (2.5%), when injected into rats'hind paw (0.05 ml), elicited a biphasic algesic responses and nitric oxide had an analgesic effect on both $A\delta$ and C sensory nerve fibers which manipulate the phases respective1y. Nitric oxides, which produced from constitutive nitric oxide synthase, activated cyclooxygenase-type I and then prostaglandins are produced from them. So, indomethacin and ibuprofen, inhibitors of COX$_1$enzyme, when pretreated intraperitoneally (100 mg/kg) could reduce the hyperalgesic state. From these results, it is possible to imagine that the intrathecally administered NO donors expressed hyperalgesia through both long-term potentiation mechanism and arachidonic acid-prostaglandin cascade.

• Environmental Mutagens and Carcinogens
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• v.22 no.3
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• pp.183-186
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• 2002

Hypertension is a multifactorial disease. Both genetic and environmental factors have been implicated in its etiology. Since the impairment of nitric oxide (NOS) production plays an important role in the pathogenesis of hypertension, endothelial nitric oxide synthase (ecNOS) gene is supposed to be a candidate gene of hypertension. Our study group investigated the 27 bp insertion/deletion (Ins/Del) polymorphism of ecNOS gene in 99 Korean normotensives and 98 hypertensives, respectively. There was no significant association with any cardiovascular risk factors as well as hypertension in Koreans. The Ins/Del polymorphism of the ecNOS gene indicated the similar allele distribution among ethnic groups studied. Further studies using larger sample size and subject information is required to describe the general picture of the association between the ecNOS gene polymorphic loci and hypertension

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.441-447
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• 2016

Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (${\alpha}_2$-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of $10^{-8}{\sim}10^{-6}mol/L$, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or $3{\times}10^{-9}mmol/L$) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial ${\alpha}_2$-adrenoceptor and nitric oxide synthase.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.199-204
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• 2012

We evaluated the role of Tat-mediated p66shc transduction on the activation of endothelial nitric oxide synthase in cultured mouse endothelial cells. To construct the Tat-p66shc fusion protein, human full length p66shc cDNA was fused with the Tat-protein transduction domain. Transduction of TAT-p66shc showed a concentration- and time-dependent manner in endothelial cells. Tat-mediated p66shc transduction showed increased hydrogen peroxide and superoxide production, compared with Tat-p66shc (S/A), serine 36 residue mutant of p66shc. Tat-mediated p66shc transduction decreased endothelial nitric oxide synthase phosphorylation in endothelial cells. Furthermore, Tat-mediated p66shc transduction augmented TNF-${\alpha}$-induced p38 MAPK phosphorylation in endothelial cells. These results suggest that Tat-mediated p66shc transduction efficiently inhibited endothelial nitric oxide synthase phosphorylation in endothelial cells.

• Journal of Trauma and Injury
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• v.21 no.1
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• pp.59-65
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• 2008

Purpose: The aim of this study was to evaluate the effect of overexpression of heat shock protein 70 (HSP70) on the expression of inducible nitric oxide synthase and on the concentration of nitric oxide and to determine the mechanism for the relationship between HSP70 and inducible nitric oxide synthase (iNOS) in sepsis. Methods: Experiments were performed on male Sprague-Dawley rats, and sepsis was induced by using cecal ligation and puncture (CLP). Glutamine (GLN) or saline was administered 1 h after initiation of sepsis. We acquired serum and lung tissues from the rats 12 h or 24 h after initiation of sepsis. We analyzed the concentration of nitric oxide, the expression of HSP70 in the lung, and the gene expression of iNOS in the lung. Results: In CLP+GLN, glutamine given after initiation of sepsis enhanced the expression of HSP70 in the lung at 12 h (CLP+GLN vs. CLP:: $47.19{\pm}10.04$ vs. $33.22{\pm}8.28$, p = 0.025) and 24 h (CLP+GLN vs. CLP: $47.06{\pm}10.60$ vs. $31.90{\pm}4.83$, p = 0.004). In CLP+GLN, glutamine attenuated the expression of iNOS mRNA in the lung at 12 h (CLP+GLN vs. CLP: $4167.17{\pm}951.59$ vs. $5513.73{\pm}1051.60$, p = 0.025) and 24 h (CLP+GLN vs. CLP: $9,437.65{\pm}2,521.07$ vs. $18,740.27{\pm}8,241.20$, p = 0.016) and reduced the concentration of nitric oxide in serum at 12 h (CLP+GLN vs. CLP: $0.86{\pm}0.48$ vs. $3.82{\pm}2.53{\mu}mol/L$, p = 0.016) and 24 h (CLP+GLN vs. CLP: $0.39{\pm}0.25$ vs. $1.85{\pm}1.70{\mu}mol/L$, p = 0.025). Conclusion: The overexpression of HSP70 induced by the administration of glutamine in sepsis attenuated the gene expression of iNOS and reduced the concentration of nitric oxide.

• Biomedical Science Letters
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• v.19 no.3
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• pp.180-187
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• 2013

Hypoxia is an integral part of the environment during luteolysis. In this study we examined whether hypoxia could directly stimulate endothelial cells to produce nitric oxide (NO). Endothelial cells were cultured in hypoxic (5% $O_2$) or normoxic (20% $O_2$) conditions and the levels of total NO, inducible NO and endothelial NO was measured. We found that hypoxia but not normoxia upregulated NO production. The increased NO levels correlated with increased inducible NO synthase (iNOS) expression whereas expression of endothelial NOS (eNOS) expression remained constant. Addition of the iNOS specific inhibitor 1400W to hypoxic cultures prevented NO production suggesting that hypoxia-induced NO production in endothelial cells was due mainly to upregulation of iNOS. We also found that prostaglandin $F_{2{\alpha}}$ (PGF) production was unaffected by hypoxia suggesting that upregulation of NO was not due to increased synthesis of PGF. In summary, we report that endothelial cells cultured under hypoxic conditions produce NO via the iNOS pathway. This study provides the importance of the relation between the hypoxic environment and the induction of NO by endothelial cells during regression of the corpus luteum in the ovary.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.233-239
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• 1995

To verify the effect of immunosuppressants on the endotoxin-induced increase in iNOS activity, the action of immunosuppressants, dexamethasone (1.5 mg/kg), azathioprine (5 mg/kg/day) and cyclosporine (10 mg/kg), were evaluated in mice pretreated with LPS. The intraperitoneal injection of lipopolysaccharide (10 mg/kg) increased the nitric oxide synthase (NOS) activity in the brain and liver to maximum at 1 and 3 hours, respectively. The increase in NOS activity was blocked by the treatment with NOS inhibitor, LNAME(300 mg/kg) and aminoguanidine(100 mg/kg); a protein inhibitor, cycloheximide (10 mg/kg); and a transcription inhibitor of inducible NOS(iNOS), dexamethasone(1.5 mg/kg). Immunosuppressants, azathioprine (5 mg/kg) and cyclosporine (10 mg/kg), effectively blocked the increase in NOS activity. These results suggest that iNOS expression plays an important role in LPS-induced the increase in NOS activity and that immunosuppressants can be used as candidate for therapeutic agents in endotoxemia.

• Korean Journal of Food Science and Technology
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• v.46 no.4
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• pp.511-515
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• 2014

In a screen for plant-derived inhibitors of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells, a flavonol isolated from the chloroform extract of Alpinia officinarum was isolated. The structure of the flavonol was found to be 3,5,7-trihydroxy-2-phenylchromen-4-one (galangin, GLG) by using spectroscopy. GLG exhibited an inhibitory effect ($IC_{50}$ value: $26.8{\mu}M$) on NO production in LPS-stimulated RAW 264.7 murine macrophage cells. Moreover, GLG suppressed expressions of inducible nitric oxide synthase (iNOS) protein and mRNA in a dose-dependent manner.