• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.345-351
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• 1998

The role of nitric oxide (NO) in the hemorrhagic hypotension was examined using a NO synthase inhibitor, $N^{\omega}-nitro-L-arginine$ methyl ester (L-NAME), in conscious rats. The rats were bled at a constant rate (2 ml/kg/min) through a femoral arterial catheter until the mean arterial pressure (MAP) was reduced by 50 mmHg. We studied the responses to hemorrhage under normal condition (Control) and after the pretreatment with 3 doses of L-NAME (1.6, 8, 40 mg/kg i.v. of NOX1.6, NOX8, and NOX40, respectively). Intravenous bolus injection of L-NAME produced a sustained increase in MAP and decrease in heart rate (HR). During hemorrhage, the MAP fell faster in the NOX8 and NOX40-treated groups than in Control group, but the control group showed same response to NOX1.6. HR greatly increased in NOX groups. The recovery from hemorrhagic hypotension was slowed in the control group, which was not treated with L-NAME. In comparison with the control group, NOX8 and NOX1.6-treated groups registered a significant recovery in MAP during the 15 min recovery period, but NOX40 brought about only a slight increase in MAP. NO precursor, L-arginine (150 mg/kg i.v.), produced significant bradycardic responses before and after hemorrhage and significant depressor response only after hemorrhagic hypotension regardless of pretreatment with L-NAME. These data suggest that the role of NO in blood pressure regulation is greater after hemorrhagic hypotension than basal condition, but the effect of NO can be detrimental to the recovery from hemorrhagic hypotension. In addition, the bradycardic response of L-arginine provides indirect evidence that NO may inhibit sympathetic activity, especially after hemorrhagic hypotension.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.281-296
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• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• Korean Journal of Exercise Nutrition
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• v.25 no.1
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• pp.16-22
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• 2021

[Purpose] Aerobic exercise training (AT) reverses aging-induced deterioration of arterial stiffness via increased arterial nitric oxide (NO) production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by AT. However, whether AT-induced changes in ADMA levels are related to changes in nitrite/nitrate (NOx) levels remains unclear. Accordingly, we aimed to clarify whether the relationship between plasma ADMA and NOx levels afected the AT-induced reduction of arterial stifness in middle-aged and older adults. [Methods] Thirty-one healthy middle-aged and older male and female subjects (66.4 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed an 8-week AT (60%-70% peak oxygen uptake [${\dot{V}}O_{2peak}$] for 45 min, 3 days/week). [Results] AT signifcantly increased ${\dot{V}}O_{2peak}$ (P < 0.05) and decreased carotid β-stifness (P < 0.01). Moreover, plasma ADMA levels were significantly decreased while plasma NOx levels and NOx/ADMA ratio were significantly increased by AT (P < 0.01). Additionally, no sex diferences in AT-induced changes of circulating ADMA and NOx levels, NOx/ADMA ratio, and carotid β-stifness were observed. Furthermore, the AT-induced increase in circulating ADMA levels was negatively correlated with an increase in circulating NOx levels (r = -0.414, P < 0.05), and the AT-induced increase in NOx/ADMA ratio was negatively correlated with a decrease in carotid β-stifness (r = -0.514, P < 0.01). [Conclusion] These results suggest that the increase in circulating NOx with reduction of ADMA elicited by AT is associated with a decrease in arterial stiffness regardless of sex in middle-aged and older adults.

• Journal of Life Science
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• v.33 no.1
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• pp.50-55
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• 2023

This study was designed to determine the activities of Rosa davurica Pall. leaf extract and their regulatory mechanisms in macrophage inflammation. Anti-inflammatory potential of Rosa davurica Pall. leaf extract was evaluated by measuring the nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) synthesis in lipopolysaccharide (LPS)-treated macrophage Raw 264.7 cells. Rosa davurica Pall. leaf extract potently inhibited LPS-induced NO release in a dose dependent manner. However, cell viability decreased to about 50% at high dose of 500 ㎍/ml, resulting in cytotoxicity. LPS-induced iNOS protein expression was also reduced significantly after treatment with Rosa davurica Pall. leaf extract. Furthermore, extract of Rosa davurica Pall. attenuated LPS-mediated phosphorylation of IκB and nuclear factor (NF-κB). Suppression of NF-κB signaling by treatment with PDTC, an NF-κB specific inhibitor, accelerated the inhibition of NO production and iNOS protein expression. These results suggest that Rosa davurica Pall. exhibits the anti-inflammatory potential in LPS-induced macrophage inflammation, partly through inhibition of NO production by down-regulation of NF-κB signaling.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.181-192
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• 1999

Background: Nitric oxide, a vasodilator synthesized from L-arginine by vascular endothelial cells, accounts for the biological activity of endothelium derived relaxing factor. Previous studies demonstrated that nitric oxide inhibitor, $N^{\omega}$-Nitro-L-Arginine(NNA) diminished the hyperdynamic splanchnic and systemic circulation in portal hypertensive rats The present study was done to determine the role of nitric oxide in the development of hyperdynamic circulations in the prehepatic portal hypertensive rat model produced by partial portal vein ligation. Methods: The portal hypertensive rats were divided into water ingestion group and NNA ingestion group. After partial portal vein ligation, NNA ingestion group and water ingestion group received NNA 1mg/kg/day and plain water through the mouth for 14 days, respectively. Cardiac output, mean arterial pressure, organ blood flow and porto-systemic shunting were measured by radioisotope labeled microsphere methods. Vascular resistances were calculated by standard equation. Results: There were significant decreases in mean arterial pressure, increases in cardiac output and cardiac index, and decreases in total systemic and splanchnic vascular resistance in portal hypertensive rats compared to normal control group (p<0.01). Compared to the water ingestion group, significantly increased mean arterial pressure with decreased cardiac output and cardiac index were developed in the NNA ingestion group. Total systemic and splanchnic vascular resistance were significantly increased in the NNA ingestion group compared to water ingestion group (p<0.05). But, there was no significant difference in portal pressure between the two groups. Conclusion: The hemodynamic results of this study indicate that hyperdynamic circulation in prehepatic portal hypertensive rat mode1 was attenuated by ingestion of NNA. Nitric oxide may play an important role in the development of hyperdynamic circulation with splanchnic vasodilation in chronic portal hypertension.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.576-587
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• 2009

Background: The up-regulation of the nitric oxide (NO)-cGMP pathway might be involved in the change of vascular reactivity in rats 3 days after they suffer acute myocardial infarction. However, the underlying mechanism for this has not been clarified. Material and Method: Acute myocardial infarction (AMI) was induced by occluding the left anterior descending coronary artery (LAD) for 30 min (Group AMI), whereas the sham-operated control rats were treated similarly without LAD occlusion (Group SHAM), The concentration-response relationships for phenylephrine (PE), KCl, acetylcholine (Ach) and sodium nitroprusside (SNP) were determined in the endothelium intact E(+) and endothelium denuded E(-) thoracic aortic rings from the rats 3 days after AMI or a SHAM operation. The concentration-response relationships of PE in the E(+) rings from the AMI rats were compared with those relationships in the rings pretreated with nitric oxide synthase (NOS) inhibitor $N{\omega}$-nitro-L-arginine methyl ester (L-NAME) or the cyclooxygenase inhibitor indomethacin. The plasma nitrite/nitrate concentrations were checked via a Griess reaction. The cyclic GMP content in the thoracic aortic rings was measured by radioimmunoassay and the endothelial nitric oxide synthase (eNOS) mRNA expression was assessed by real time PCR. Result: The mean infarct size (%) in the rats with AMI was $21.3{\pm}0.62%$. The heart rate and the systolic and diastolic blood pressure were not significantly changed in the AMI rats. The sensitivity of the contractile response to PE and KCl was significantly decreased in both the E(+) and E(-) aortic rings of the AMI group (p<0.05). L-NAME completely reversed these contractile responses whereas indomethacin did not (p<0.05). Moreover, the sensitivity of the relaxation response to Ach was also significantly decreased in the AMI group (p<0.05). The plasma nitrite and nitrate content (p<0.05), the basal cGMP content (p<0.05) and the eNOS mRNA expression (p=0.056) in the AMI rats were increased as compared with the SHAM group. Conclusion: Our findings indicate that the increased eNOS activity and the up-regulation of the NO-cGMP pathway can be attributed to the decreased contractile or relaxation response in the rat thoracic aorta 3 days after AMI.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.265-274
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• 2001

Purpose : Proctitis is one of acute complications encountered when radiotherapy was appled to the pelvis. Radiation-induced proctitis represents similar microscopic findings that are observed in inflammatory bowel disease (IBD). Nitric oxide (NO) plays an important role in the inflammatory process and many data suggest a close relationship between NO production and gastrointestinal inflammation. This study was aimed to establish the optimal radiation dose for radiation-induced proctitis in rat and to find a relationship between radiation proctitis and NO production. Materials and methods : Female Wistar rats, weighing from 150 to 220 g, received various doses(10-30 Gy) of radiation to the rectum. On the 5th and 10th day after irradiation, rectal specimens were evaluated grossly and microscopically. In addition, the degree of NO production by irradiation dose was evaluated by study with NOS expression and nitrite production in the irradiated rectal tissue. To evaluate relationship between radiation proctitis and NO, we administered aminoguanidine, iNOS inhibitor and L-arginine, substrate of NOS to rats from 2 days before to 7 days after the irradiation. Results : There were obvious gross and hostological changes after 17.5 Gy or higher radiation dose but not with 15 Gy or less radiation dose. Twenty Gy or higher dose of radiation caused Grade 4 damage in most of rectal specimens which were more likely to be related to the late complications such as fibrosis, rectal bleeding and rectal obstruction. A single fraction of 17.5 Gy to the rat rectum is considered to be an optimal dose to produce commonly experienced proctitis in the clinic. The result demonstrated that severity of microscopic damage of rectal mucosa from irradiation significantly correlated with iNOS over-expression. However, administration of iNOS inhibitor or substrate of iNOS did not influence the degree of rectal damage. Conclusion : A single fraction of 17.5 Gy irradiation to the rat rectum considered to be an optimal dose for radiation induced proctitis model. These results indicated that an excess production of NO contributes to pathogenesis of radiation-induced proctitis in part but was not the direct cause of rectal damage.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.178-187
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• 2006

Objectives : Peroxynitrite $(ONOO^-),\;{\cdot}O_2^-$ and nitric oxide (NO) are cytotoxic species that can oxidize several cellular components such as proteins, lipids and DNA. It has been implicated in the aging process and age-related disease such as Alzheimer's disease, rheumatoid arthritis, cancer and atherosclerosis. The aim of this study was to investigate $ONOO^-$ scavengactivities, and that of its precursors, NO and ${\cdot}O_2^-$ of Samjunghwan. Methods : To investigate $ONOO^-,\;NO,\;{\cdot}O_2^-$ scavenging activities, fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Results : Samjunghwan markedly scavenged authentic $ONOO^-,\;{\cdot}O_2^-$ and NO. It also inhibited $ONOO^-$ induced by .02' and NO which are derived from SIN-I. Furthermore, Samjunghwan inhibited $ONOO^-$, ${\cdot}O_2^-$ and NO generation in LPS-treated ICR mouse kidney postmitochondria. Conclusions : These results suggest that Samjunghwan is an effective $ONOO^-,\;{\cdot}O_2^-$ and NO scavenger, and that this substance has a potential role as an inhibitor of aging process, and in therapy against age-related diseases.

• Fisheries and Aquatic Sciences
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• v.15 no.4
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• pp.293-297
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• 2012

${\gamma}$-Aminobutyric acid-enriched sea tangle extract was obtained from the fermentation of Lactobacillus brevis BJ-20. The fermented sea tangle extract (FST) was separated into three fractions by molecular weight: FST I (greater than 10 kDa), FST II (1-10 kDa), and FST III (less than 1 kDa). The anti-inflammatory characteristics of the FST fractions were investigated by measuring the production of nitric oxide (NO) and the expression levels of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced mouse macrophage (RAW 264.7) cells. Both NO production and iNOS expression levels were significantly inhibited by FST treatments in a dose-dependent manner. FST III was the most effective inhibitor of processes. This demonstrates that the effect of FST on LPS-induced inflammation might be closely correlated with the inhibition of inflammatory cytokine expression.

• YAKHAK HOEJI
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• v.38 no.2
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• pp.184-190
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• 1994

The activities of nitric oxide synthase and the contents of methylarginines were investigated in the pancreatic tissues of various animals by citrulline-forming method and HPLC, respectively. The high level of in vitro NO synthase activity was detected in chicken pancreas whereas MMA, the strong competitive inhibitor for NO synthase, was detected as trace in the same tissue. On the other hand, the low level of NO synthase activity was observed in the porcine pancreas while the contents of MMA were high. However, it was not possible to find any relationship between NO synthase activities and the contents of dimethylarginines at present time. D'MA was equally distributed among the pancreatic tissues of various animals but DMA was not.