• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.136-140
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• 1994

To prove the hypothesis that NO- and N $O_2$-carrying molecules potentiate photorelaxation by generating NO, investigation was carried out using isolated rabbit and human corpus cavernosum. Corporal smooth muscle, in the presence or absence of endothelium, relaxed only slightly upon ultraviolet light (366 nm) irradiation. But, NO-and/or N $O_2$-containing compounds such as streptozotocin and $N^{G}$-nitro-L-arginine methyl ester significantly (p<0.01) enhanced photorelaxation in this tissue. In addition, $N^{G}$-nitro-D-arginine methyl ester, known to lack inhibitory action on NO synthase, showed concentration-dependent potentiation of the photorelaxation. Oxygen radical generating system via copper＋ascorbic acid and guanylate cyclase inhibitor, methylene blue, significantly (p<0.05) inhibited the streptozotocin-potentiated photorelaxation. Nitrite was accumulated by photolysis of streptozotocin, $N^{G}$-nitro-L-arginine methyl ester and $N^{G}$-nitro-D-arginine methyl ester, in a concentration and exposure time dependent manner. These observations indicate that NO is a potent relaxant of rabbit and human corpus cavernosum and further support the hypothesis that NO is released by photolysis from NO- and N $O_2$-carrying molecules.lecules.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.389-397
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• 1996

Gatric mucosa is exposed to toxic, reactive oxygen species generated within the lumen. Nitric oxide protected acetaminophen-induced hepatotoxicity by maintaining glutathione homeostasis. The present study examined the role of nitric oxide in mediating hydrogen peroxide - induced damage to gastric cells. Hydrogen peroxide was generated by glucose oxidase acting on ${\beta}-D-glucose$. L-arginine, $N^G-nitro-L-arginine$ methyl ester, or $N^G-nitro-L-arginine$ were treated to the cells with glucose/glucose oxidase. Lipid peroxidation and nitrite release and cellular content of glutathione were determined. As a result, dose - dependent increase in lipid peroxide production as well as dose - dependent decrease in nitrite release and cellular glutathione content were observed in glucose/glucose oxidase - treated cells. Pretreatment of L-arginine, a substrate for nitric oxide synthase, prevented the increase of lipid peroxide production and the reduction of nitrite release as well as glutathione content. Inhibitors of nitric oxide synthase such as $N^G-nitro-L-arginine$ methyl ester and $N^G-nitro-L-arginine$ did not protect hydrogen peroxide - induced cell damage. In conclusion, nitric oxide protects gestric cells from hydrogen peroxide possibly by inhibiting lipid peroxidation and by preserving cellular glutathione stores.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.397-403
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• 1999

The present study examined the effect of a methanol extract of Evodiae Fructus on the cardiovascular function in N-nitro-L-arginine methyl ester (NAME)-induced hypertensive Wistar rats after treatment over 6 weeks. In rats treated with NAME, blood pressure, weight of heart, aorta media thickness and media/lumen ratio significantly (p<0.05) increased, whereas coronary flow and heart rate of isolated heart significantly (p<0.05) decreased compared with control group at 6 weeks. In rats treated with NAME and Evodiae Fructus, blood pressure, aorta media/lumen ratio significantly(p<0.05) decreased compared with NAME treated group at 6 weeks. These results suggest that Evodiae Fructus is applicable to the treatment of hypertension and vascular hypertrophy.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.199-207
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• 1998

Ginseng saponin (G5) purified from Panax ginseng, increase renal blood flow in rats. Nitric oxide (NO) is thought to be a substance endogenously released by G5 in preconstricted lungs and cultured endothelial cells. The present study aims to determine whether G5 could stimulate endogenous 1'elease of NO in rat kidney and urine levels of the stable NO metabolites, nitrite (NO,) and nitrate (NO,) and urinary COMP levels were measured 8 hr after a single intraperitoneal injection of GS (200 mg/kg) Into rats. The effects of the WO synthesis inhibitor, Nu-nitro-L-arginine methyl ester, .1nd the NO precursor, L-arginine, on the G5-induced changes were also determined. The activity of NO synthase, as determined by conversion of ('"C)-L-arginine to ('"C)-L-citrulline, in whole kidney, glomeruli and cortical tubules were also investigated. A single injection of GS resulted in endogenous production of NO as reflected by increase in serum and urine levels of N021N03 and urinary cGMP levels, which were inhibited by the addition o ( N-nitro-L-arginine methyl ester and restored fly L-arginine. GS also stimulated the activity of NO synthase in whole kidney as well as glomeruli and cortical tubules, and Nu-nitro-L-arginine methyl tilter significantly prevented this increase. In conclusion, GS stimulates endogenous NO production and thus, may play a protective role 1 11 the kidney by modulating renal blood flow.

• The Korean Journal of Pain
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• v.19 no.2
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• pp.142-145
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• 2006

Background: Nitric oxide (NO) is involved in the transmission and modulation of nociceptive information at the peripheral, spinal cord and supraspinal levels. We conducted this experiment to assess the antinociceptive effects of a nonselective nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the modulation of pain in rats subjected to the formalin test. Methods: Formalin 5% was injected in the right hind paw after intraperitoneal (IP) injection of various doses of L-NAME (0.5 mg/kg, 1.5 mg/kg with and without L-arginine 100 mg/kg, 5.0 mg/kg). The number of flinches was measured. Results: Formalin injected into the rat hind paw induced a biphasic nociceptive behavior. IP injected L-NAME diminished the nociceptive behaviors in a dose-dependent manner during phases 1 and 2. The concomitant injection of L-arginine reversed the antinocipetive effect of L-NAME. Conclusions: The data demonstrates that a nonselective NOS inhibitor, L-NAME, possesses antinociceptive properties in rats subjected to the formalin test, and the antinociceptive effect of L-NAME is reversed by the concomitant administration of L-arginine.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.511-519
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• 1998

This study investigated the role of nitric oxide on the oxidative damage in gastric mucosa of rats which received ischemia/reperfusion and its relation to mucus. Nitric oxide synthesis modulators such as L-arginine and $N^G-nitro-L-arginine$ methyl ester, and sodium nitroprusside, a nitric oxide donor, were injected intraperitoneally to the rats 30 min prior to ischemia/reperfusion which was induced by clamping the celiac artery and the superior mesenteric artery for 30 min and reperfusion for 1 h. Lipid peroxide production, the contents of glutathione and mucus, and glutathione peroxidase activities of gastric mucosa were determined. Histological observation of gastric mucosa was performed by using hematoxylin-eosin staining and scanning electron microscopy. The result showed that ischemia/reperfusion increased lipid peroxide production and decreased the contents of glutathione and mucus as well as glutathione peroxidase activities of gastric mucosa. Ischemia/reperfusion induced gastric erosion and gross epithelial disruption of gastric mucosa. Pretreatment of L-arginine, a substrate for nitric oxide synthase, and sodium nitroprusside prevented ischemia/reperfusion-induced alterations of gastric mucosa. However, $N^G-nitro-$ L- arginine methyl ester, a nitric oxide synthase inhibitor, deteriorated oxidative damage induced by ischemia/reperfusion. In conclusion, nitric oxide has an antioxidant defensive role on gastric mucosa by maintaining mucus, glutathione, and glutathione peroxidase of gastric mucosa.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.4
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• pp.213-216
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• 2006

The present study was aimed to determine whether nitric oxide (NO) plays a role in the regulation of aquaporin (AQP) channels in the kidney. Male Brattleboro rats ($250{\sim}300\;g$ body weight) were used. The experimental group was treated with $N^G$-nitro-L-arginine methyl ester (L-NAME, 100 mg/L drinking water) for 1 week, and cotreated with indomethacin (5 mg/kg, twice a day, i.p.) for the last two days. Control groups were treated with either L-NAME for 1 week, indomethacin for 2 days, or without any drug treatment. The abundance of AQP1, AQP2 and AQP3 proteins in the kidney was determined by Western blot analysis. Indomethacin downregulated AQP channels, whereas L-NAME by itself showed no significant effects on them. The indomethacin-induced downregulation of AQP2 and AQP3 was significantly blunted in L-NAME-treated rats, while that of AQP1 was not affected. These results suggest that endogenous NO, when stimulated, may downregulate AQP channels that are specifically regulated by AVP/cAMP pathway in the kidney.

• Journal of Korean Neurosurgical Society
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• v.38 no.4
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• pp.287-292
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• 2005

Objective : Kainic acid[KA] enhances the expression of nitric oxide synthase, increases nitric oxide[NO], and thus evokes epileptic convulsion, which results in neuronal damage in the rat brain. NO may stimulate cyclooxygenase type-2 [COX-2] activity, thus producing seizure and neuronal injury, but it has also been reported that KA-induced seizure and neurodegeneration are aggravated on decreasing the COX-2 level. This study was undertaken to investigate whether the suppression of NO using the NOS inhibitor, N-nitro-L-arginine methyl ester[L-NAME], suppresses or enhances the activity of COX-2. Methods : Silver impregnation and COX-2 immunohistochemical staining were used to localize related pathophysiological processes in the rat forebrain following KA-induced epileptic convulsion and L-NAME pretreatment. Post-injection survival of the rat was 1, 2, 3days and 2months, respectively. Results : After the systemic administration of KA in rats, neurodegeneration increased with time in the cornu ammonis [CA] 3, CA 1 and amygdala, as confirmed by silver impregnation. On pretreating L-NAME, KA-induced neuronal degeneration decreased. COX-2 enzyme activities increased after KA injection in the dentate gyrus, CA 3, CA 1, amygdala and pyriform cortex, as determined by COX-2 staining. L-NAME pretreatment prior to KA-injection, caused COX-2 activities to increase compared with KA- injection only group by 1day and 2days survival time point. Conclusion : These results suggest that L-NAME has a neuroprotective effect on KA-induced neuronal damage, especially during the early stage of neurodegeneration.

• Journal of Applied Biological Chemistry
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• v.62 no.3
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• pp.265-273
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• 2019

This study aimed to evaluate the anti-atherosclerotic and anti-hypertensive effects of six different plant extracts using a N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced rat model of hypertension. All extracts were administered orally for six weeks. At the end of the study period blood pressure, blood flow, aortic histopathology, and hepatic endothelial nitric oxide synthase (eNOS) expression were measured. Subsequently, we also measured the levels of intracellular reactive oxygen species, nitric oxide (NO), and anti-inflammatory cytokines in vitro. Based on these screening results, we selected extracts of Cinnamomum cassia (C. cassia) and Salvia miltiorrhiza (S. miltiorrhiza) for further evaluation. C. cassia and S. miltiorrhiza extracts ameliorated hypertension and atherosclerosis in L-NAME-treated rats in a dose-dependent manner. In addition, a mixture of C. cassia and S. miltiorrhiza had an additive effect to reduce blood pressure, increase blood flow, and normalize aortic tissue. This mixture demonstrated anti-oxidative and anti-inflammatory activities in vitro. In conclusion, although further analysis of the therapeutic mechanism is required, the anti-hypertensive and anti-atherosclerotic effects of this mixture are likely mediated by increased eNOS expression, and its anti-oxidative and anti-inflammatory activities.

• The Korean Journal of Physiology
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• v.28 no.2
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• pp.225-231
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• 1994

The present study was undertaken to investigate the role of endogenous nitric oxide in renin release under different physiological conditions. In the first series of experiments, renin release was either inhibited by acute volume-expansion (VE) or stimulated by clipping one renal artery in the rat. VE was induced by intravenous infusion of saline (0.9% NaCl) up to 5% of the body weight over 45 min under thiopental (50 mg/kg, IP) anesthesia. VE caused a decrease of plasma renin concentration (PRC). With $N^G-nitro-L-arginine$ methyl ester $(L-NAME,\;5\;{\mu}g/kg\;per\;min)$ superadded to VE, PRC decreased further. The magnitude of increase in plasma atrial natriuretic peptide levels following VE was not affected by the L-NAME. In two-kidney, one clip rats, L-NAME-supplementation resulted in a decrease, and L-arginine-supplementation an increase of PRC. Plasma atrial natriuretic peptide levels were significantly lower in the L-arginine group than in the control. Blood pressure did not differ among the L-NAME, L-arginine, and control groups. In another series of experiments, the renin response to a blockade of NO synthesis was examined using in vitro preparations from isolated renal cortex. L-NAME significantly increased basal renin release, although it was without effect on the isoproterenol-stimulated release. These findings suggest that endogenous nitric oxide significantly contributes to the renin release. Since many factors may affect the renin release in vivo, an interaction between NO and renin under various pathophysiological states is to be further defined.