• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.41-46
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• 2001

To investigate the mutual relationship between angiotensin II (Ang II) and nitric oxide (NO) in paraventricular nucleus (PVN), Ang II receptor type Ia $(AT_{1A}),$ type Ib $(AT_{1B}),$ endothelial constitutive nitric oxide synthase (ecNOS), and neuronal constitutive nitric oxide synthase (ncNOS) mRNA levels of rat PVN were measured after unilateral carotid artery ligation. $AT_{1A}$ and $AT_{1B}$ mRNA levels were markedly elevated 6 hrs after unilateral carotid artery ligation. Losartan injection $(10\;{\mu}g/0.3\;{\mu}l)$ into the PVN augmented of the increment of $AT_{1A}$ and $AT_{1B}$ mRNAs It also increased ecNOS gene expression. In addition, $AT_{1B}$ mRNA levels increased after N-nitro-L-arginine methyl ester (L-NAME) injection $(50\;{\mu}g/0.3\;{\mu}l)$ into the PVN. These results suggest that Ang II and NO in the rat PVN may interplay, at least in part, through regulation of gene expression of ecNOS and $AT_{1B},$ respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.123-128
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• 2011

Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood circulation and removing stasis. During a screening procedure on medicinal plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed inhibitory activity on arginase which has recently been reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE reciprocally increased NOx production through enhancement of eNOS dimer stability without any significant changes in the protein levels of eNOS and arginase II expression. Furthermore, CLE-dependent arginase inhibition resulted in increase of NO generation and decrease of superoxide production on endothelium of isolated mice aorta. These results indicate that CLE augments NO production on endothelium through inhibition of arginase activity, and may imply their usefulness for the treatment of cardiovascular diseases associated with endothelial dysfunction.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.171.1-171.1
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• 2003

In some tissues 17b-estradiol (E2) is known to increase endothelial NOS expression. In the present study we examined the effects of E2 on estrogen receptors (ERa and b) and inducible nitric oxide synthase (iNOS) expression and analyzed the mechanisms in rat peritoneal macrophages. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.9-20
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• 2023

The mechanism is unclear for the reported protective effect of hyperbaric oxygen preconditioning against oxidative stress in tissues, and the distinct effects of hyperbaric oxygen applied after stress. The trained mice were divided into three groups: the control, hyperbaric oxygenation preconditioning, and hyperbaric oxygenation applied after mild (fasting) or hard (prolonged exercise) stress. After preconditioning, we observed a decrease in basal levels of nitric oxide, tetrahydrobiopterin, and catalase despite the drastic increase in inducible and endothelial nitric oxide synthases. Moreover, the basal levels of glutathione, related enzymes, and nitrosative stress only increased in the preconditioning group. The control and preconditioning groups showed a similar mild stress response of the endothelial and neuronal nitric oxide synthases. At the same time, the activity of all nitric oxide synthase, glutathione (GSH) in muscle, declined in the experimental groups but increased in control during hard stress. The results suggested that hyperbaric oxygen preconditioning provoked uncoupling of nitric oxide synthases and the elevated levels of GSH in muscle during this study, while hyperbaric oxygen applied after stress showed a lower level of GSH but higher recovery post-exercise levels in the majority of antioxidant enzymes. We discuss the possible mechanisms of the redox response and the role of the nitric oxide in this process.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.539-545
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• 2016

Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function.

• Journal of Ginseng Research
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• v.40 no.3
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• pp.285-291
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• 2016

Background: Ginsenosides have been shown to exert beneficial pharmacological effects on the central nervous, cardiovascular, and endocrine systems. We sought to determine whether total ginsenosides (TG) inhibit monocrotaline (MCT)-induced pulmonary hypertension and to elucidate the underlying mechanism. Methods: MCT-intoxicated rats were treated with gradient doses of TG, with or without $N^G$-nitro-$\small{L}$-arginine methyl ester. The levels of molecules involving the regulation of nitric oxide and mitogen-activated protein kinase pathways were determined. Results: TG ameliorated MCT-induced pulmonary hypertension in a dose-dependent manner, as assessed by the right ventricular systolic pressure, the right ventricular hypertrophy index, and pulmonary arterial remodeling. Furthermore, TG increased the levels of pulmonary nitric oxide, endothelial nitric oxide synthase, and cyclic guanosine monophosphate. Lastly, TG increased mitogen-activated protein kinase phosphatase-1 expression and promoted the dephosphorylation of extracellular signal-regulated protein kinases 1/2, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase 1/2. Conclusion: TG attenuates MCT-induced pulmonary hypertension, which may involve in part the regulation of nitric oxide and mitogen-activated protein kinase pathways.

• Korean Journal of Veterinary Research
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• v.41 no.3
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• pp.269-273
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• 2001

The expression of protein kinase C(PKC) isoforms and nitric oxide synthase (NOs) isoforms was studied in the equine vomeronasal organ(VNO), a pheromone receptor organ, using immunohistochemistry. All PKC isoforms including PKC $\alpha$, ${\beta}I$, $\delta$, and $\theta$ were detected in the supporting cells, sensory receptor cells, and basal sensory epithelial cells, while constitutive PKC $\alpha$ and ${\beta}I$ were stained more intensely than novel PKC $\delta$ and ${\theta}$. There was also a varying degree of immunostaining for PKCs in the glandular acini and VNO nerve. Constitutive neuronal and endothelial NOSs, and inducible NOS were detected in the VNO sensory epithelia. There was intense immunoreactivity for endothelial NOS in the VNO sensory epithelia but weak reactivity for neuronal NOS, while inducible NOS showed little immunoreactivity in the adjacent section. These findings suggest that both PKCs and NOSs may be involved in the process of pheromone reception in the horse. Constitutive isoforms of these enzymes may play a more important role in signal trasduction in the VNO of the horse.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.155-161
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• 2001

Background and Objectives: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. This reaction is catalyzed by nitric oxide synthase (NOS). NO is an important bioactive agent and a signalling molecule that mediates a variety of biologic actions such as vasodilation, neurotransmission, host defense, and iron metabolism but increased NO production may also contribute to the pathogenesis of a various of disorders, including cancer. Before now, the role of NO in thyroid gland is still investigated and it was supposed that NO mediate the angiogenesis in tumor growth. Others journal and works identified the expression of iNOS that involve by neutrophil and eNOS that involve in part in the vascular remodeling and to understand the role of NO in human thyroid gland. But authors revealed only eNOS in thyroid neoplasm. iNOS was identifed by inflammation in fault. Materials and Methods: Western blot analysis was performed, using a polyclonal antibody against eNOS (Rabbit polyclonal IgG). Using the same antibody, the distribution of eNOS was examined in 15 formalin-fixed paraffin embedded samples by immunohistochemistry. By NADPH consumption rate, NOS activity was estimated at nodular hyperplasia. Results: Western blot analysis exhibited that eNOS was significantly elevated in thyroid papillary carcinoma, compared to that in nodular hyperplasia and normal tissue. Immunohistochemistry showed that the immunoreacitivity was present more significantly in thyroid follicular epithelial cell layer than vascular endothelial cell. NOS activity increased in nodular hyperplasia. Conclusions: Thyroid papillary cancer without neutrophil invasion expressed only eNOS. The endothelial localization of eNOS may play an important role in pathogenensis of human thyroid nodular hyperplasia and the follicular localization of thyroid papillary carcinomas.

• BMB Reports
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• v.50 no.7
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• pp.384-389
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• 2017

The Nogo-B receptor (NgBR) is necessary for not only Nogo-B-mediated angiogenesis but also vascular endothelial growth factor (VEGF) -induced angiogenesis. However, the molecular mechanisms underlying the regulatory role of the VEGF-NgBR axis in angiogenesis are not fully understood. Here, we report that miR-26a serves as a critical regulator of VEGF-mediated angiogenesis through directly targeting NgBR in endothelial cells (ECs). Stimulation of ECs by VEGF increased the expression of NgBR and decreased the expression of miR-26a. In addition, miR-26a decreased the VEGF-induced migration and proliferation of ECs. Moreover, miR-26a overexpression in ECs decreased the VEGF-induced phosphorylation of the endothelial nitric oxide synthase (eNOS) and the production of nitric oxide, which is important for angiogenesis. Overall, these data suggest that miR-26a plays a key role in VEGF-mediated angiogenesis through the modulation of eNOS activity, which is mediated by its ability to regulate NgBR expression by directly targeting the NgBR 3'-UTR.

• Applied Microscopy
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• v.38 no.3
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• pp.221-233
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• 2008

Endogenous nitric oxide (NO) has been known to regulate many physiological and pathological processes, especially the glandular secretion and blood flow. However, nitric oxide synthase (NOS) responsible for NO synthesis has not been well studied ultrastructurally in rat salivary gland. The present study was performed to investigate the distribution of nitric Oxide synthase isoforms (endothelial. neuronal, and inducible NOS). Immunoelectron microscopic study, using monoclonal mouse anti-endothelial NOS, anti-neuronal NOS, and anti-inducible NOS, was performed in the salivary gland of rat. Endothelial NOS (eNOS)-positive immunoreactivities were most prominent in the secretory granules of serous cells of the salivary gland of the rat. Immunoreactivities were well concentrated on serous secretory granules in the serous cells. However, weak eNOS-positive immunoreactivity was observed in the mucous secretory granules of the mucous cells. Positive endothelial NOS (eNOS) immunoreactivities were most prominent in the secretory granules of intralobular ducts. Ductal secretory granules and acinar serous secretory granules have a similar pattern of labeling as eNOS suggestings. Neural NOS (nNOS)-positive immunoreactivity was not detected in duct systems or in acinar cells. Inducible NOS (iNOS)-positive immunoreactivity was not seen in acinar and ductal cells. These results reveal the presence of eNOS in the salivary gland of the rat, which may be related with regulation of the glandular secretion and blood flow through the gland.