• Title, Summary, Keyword: endothelial nitric oxide synthase

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Elevation of Nitric Oxide Synthase Activity by Dimethyladenosine from Silkworm Pupae in Aged Rats

  • Ahn, Mi-Young;Han, Jea-Woong;Hong, Yoo-Na;Hwang, Jae-Sam
    • Toxicological Research
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    • v.24 no.3
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    • pp.169-174
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    • 2008
  • This study examined the mechanisms underlying the effects of the vasorelaxation active substance(VAS), dimethyladenosine-5'-L-arabinose, and its partial purification fraction on nitric oxide synthase in improving erectile dysfunction with particular focus on the nitric oxide (NO)-cGMP pathways. Two rat models, 9-month-old SD rats and 11-month-old SD rats, were given VAS(40 mg/kg per day) for 4 days, The aqueous fraction of silworm male pupae extract; semi-purified VAS(100 mg/kg per day) for 10 days, respectively. The NOS activities of the following three enzymes were examined: neuronal NO synthase(nNOS), inducible NOS(iNOS), endothelial NOS(eNOS), vascular endothelial growth factor on endothelial cells(VEGF) and anti-inflammation effect of Tumor necrosis factor-$\alpha$. The results showed increases in the nitric oxide synthase activities. Western blotting of the tissue homogenate showed an increase in the nNOS level in the brain and tongue, and an increase in the endothelial NO synthase(eNOS) level in penis. However, there was little association with VEGF production in HUVEC endothelial cells and no relationship with TNF-$\alpha$ which showed low levels.

Expression and localization of endothelial and inducible nitric oxide synthase in bovine uterus (소 자궁에서 endothelial nitric oxide synthase(NOS) 및 inducible NOS의 발현)

  • Lee, Yongduk;Kim, Seungjoon;Moon, Changjong;Shin, Taekyun
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.551-554
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    • 2003
  • Nitric oxide synthase (NOS) has been reported in uterus. We examined the expression of the NOS isoforms, constitutive endothelial (eNOS) and inducible NOS (iNOS), in bovine uterus by immunohistochemistry. eNOS immunoreactivity was localized predominantly to the endothelial cells that line uterine microvessels and to endometrial glandular epithelial cells, but was barely detectable in endometrial stromal cells. iNOS immunostaining was detected in glandular epithelial and stromal cells in the endometrium and in the endothelial cells of myometrial blood vessels. These findings suggest that both eNOS and iNOS may play important roles in the physiology of the uterus, possibly by generating NO.

Hypoxia Enhances Nitric Oxide Synthesis by Upregulation of Inducible Nitric Oxide Synthase in Endothelial Cells

  • Rhee, Ki-Jong;Gwon, Sun-Yeong;Lee, Seunghyung
    • 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.

Tat-Mediated p66shc Transduction Decreased Phosphorylation of Endothelial Nitric Oxide Synthase in Endothelial Cells

  • Lee, Sang-Ki;Lee, Ji-Young;Joo, Hee-Kyoung;Cho, Eun-Jung;Kim, Cuk-Seong;Lee, Sang-Do;Park, Jin-Bong;Jeon, Byeong-Hwa
    • 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.

Korean red ginseng inhibits arginase and contributes to endothelium-dependent vasorelaxation through endothelial nitric oxide synthase coupling

  • Shin, Woosung;Yoon, Jeongyeon;Oh, Goo Taeg;Ryoo, Sungwoo
    • Journal of Ginseng Research
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    • v.37 no.1
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    • pp.64-73
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    • 2013
  • Korean red ginseng water extract (KG-WE) has known beneficial effects on the cardiovascular system via inducting nitric oxide (NO) production in endothelium. Endothelial arginase inhibits the activity of endothelial nitric oxide synthase (eNOS) by substrate depletion, thereby reducing NO bioavailability and contributing to vascular diseases including hypertension, aging, and atherosclerosis. In the present study, we demonstrate that KG-WE inhibits arginase activity and negatively regulates NO production and reactive oxygen species generation in endothelium. This is associated with increased dimerization of eNOS without affecting the protein expression levels of either arginase or eNOS. In a vascular tension assay, when aortas isolated from wild type mice were incubated with KG-WE, NO-dependent enhanced vasorelaxation was observed. Furthermore, KG-WE administered via by drinking water to atherogenic model mice being fed high cholesterol diet improved impaired vascular function. Taken together, these results suggest that KG-WE may exert vasoprotective effects through augmentation of NO signaling by inhibiting arginase. Therefore, KG-WE may be useful in the treatment of vascular diseases derived from endothelial dysfunction, such as atherosclerosis.

The Distribution of the Insertion/Deletion Polymorphism of the Endothelial Nitric Oxide Gene in Koreans (한국인에서 Endothelial Nitric Oxide Synthase 유전자의 Insertion/Deletion Polymorphism의 분포)

  • 김선정;강병용;배준설;김기태;이강오
    • 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

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Regulation of NO from Endothelial Cells by the Decrease of Cellular cAMP Under Arsenite Exposure

  • Lee, Soo-Youn;Min, Ji-Ho
    • Journal of Microbiology and Biotechnology
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    • v.18 no.2
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    • pp.392-395
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    • 2008
  • In an attempt to delineate the direct effect of arsenite-induced endothelial dysfunction on nitric oxide (NO) production, confluent bovine aortic endothelial cells (BAEC) were incubated with arsenite, and endothelial NO synthase expression and NO production were measured. Exposure of arsenite decreased NO production for up to 24h. This decrease was accompanied by decreases in cAMP, protein kinase A (PKA) activity, and furthermore, significant reduction of pCREB. In conclusion, this study is the first to demonstrate that exposure of arsenite decreases NO production by a reduction of pCREB and PKA activity that may be mediated by cAMP, leading to endothelial dysfunction.

Impaired Endothelium-Dependent Relaxation is Mediated by Reduced Production of Nitric Oxide in the Streptozotocin-Induced Diabetic Rats

  • Park, Kyoung-Sook;Kim, Cuk-Seong;Kang, Sang-Won;Park, Jin-Bong;Kim, Kwang-Jin;Chang, Seok-Jong;Jeon, Byeong-Hwa
    • 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.

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Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase

  • Nong, Lidan;Ma, Jue;Zhang, Guangyan;Deng, Chunyu;Mao, Songsong;Li, Haifeng;Cui, Jianxiu
    • 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.

Intravenous administration of piceatannol, an arginase inhibitor, improves endothelial dysfunction in aged mice

  • Nguyen, Minh Cong;Ryoo, Sungwoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.83-90
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    • 2017
  • Advanced age is one of the risk factors for vascular diseases that are mainly caused by impaired nitric oxide (NO) production. It has been demonstrated that endothelial arginase constrains the activity of endothelial nitric oxide synthase (eNOS) and limits NO generation. Hence, arginase inhibition is suggested to be vasoprotective in aging. In this study, we examined the effects of intravenous injection of Piceatannol, an arginase inhibitor, on aged mice. Our results show that Piceatannol administration reduced the blood pressure in aged mice by inhibiting arginase activity, which was associated with NO production and reactive oxygen species generation. In addition, Piceatannol administration recovered $Ca^{2+}$/calmodulin-dependent protein kinase II phosphorylation, eNOS phosphorylation and eNOS dimer stability in the aged mice. The improved NO signaling was shown to be effective in attenuating the phenylephrine-dependent contractile response and in enhancing the acetylcholine-dependent vasorelaxation response in aortic rings from the aged mice. These data suggest Piceatannol as a potential treatment for vascular disease.