scholarly journals Peroxynitrites and impaired modulation of nitric oxide concentrations in embryos from diabetic rats during early organogenesis

Reproduction ◽  
2005 ◽  
Vol 130 (5) ◽  
pp. 695-703 ◽  
Author(s):  
A Jawerbaum ◽  
R Higa ◽  
V White ◽  
E Capobianco ◽  
C Pustovrh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Maternal Diabetes ◽  
Inhibitory Effect ◽  
Signaling Molecules ◽  
Diabetic Rats ◽  
Prostaglandin E ◽  
No Production ◽  
Diabetic Embryopathy ◽  
And Function

Maternal diabetes significantly increases the risk of congenital malformation, a syndrome known as diabetic embryopathy. Nitric oxide (NO), implicated in embryogenesis, has been found elevated in embryos from diabetic rats during organogenesis. The developmental signaling molecules endothelin-1 (ET-1) and 15-deoxy Δ12,14prostaglandin J2 (15dPGJ2) downregulate embryonic NO levels. In the presence of NO and superoxide, formation of the potent oxidant peroxynitrite may occur. Therefore, we investigated peroxynitrite-induced damage, ET-1 and 15dPGJ2 concentrations, and the capability of ET-1, 15dPGJ2 and prostaglandin E2 (PGE2) to regulate NO production in embryos from severely diabetic rats (streptozotocin-induced before pregnancy). We found intense nitrotyrosine immunostaining (an index of peroxynitrite-induced damage) in neural folds, neural tube and developing heart of embryos from diabetic rats (P < 0.001 vs controls). We also found reduced ET-1 (P < 0.001) and 15dPGJ2 (P < 0.001) concentrations in embryos from diabetic rats when compared with controls. In addition, the inhibitory effect of ET-1, 15dPGJ2 and PGE2 on NO production found in control embryos was not observed in embryos from severely diabetic rats. In conclusion, both the demonstrated peroxynitrite-induced damage and the altered levels and function of multiple signaling molecules involved in the regulation of NO production provide supportive evidence of nitrosative stress in diabetic embryopathy.

Sources and implications of basal nitric oxide in spontaneous contractions of guinea pig taenia caeci

2003 ◽  
Vol 285 (4) ◽  
pp. G747-G753 ◽  
Author(s):  
Catalina Caballero-Alomar ◽  
Carmen Santos ◽  
Diego Lopez ◽  
M. Teresa Mitjavila ◽  
Pere Puig-Parellada
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Inhibitory Effect ◽  
No Production ◽  
Paramagnetic Resonance ◽  
Synthase Inhibitor ◽  
Spontaneous Contractions ◽  
Electron Paramagnetic

We examined in vitro the source and role of basal nitric oxide (NO) in proximal segments of guinea pig taenia caeci in nonadrenergic, noncholinergic (NANC) conditions. Using electron paramagnetic resonance (EPR), we measured the effect of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10–4 M), the neuronal blocker tetrodotoxin (TTX, 10–6 M), or both on spontaneous contractions and on the production of basal NO. Both l-NAME and TTX, when tested alone, increased the amplitude and frequency of contractions. NO production was abolished by l-NAME and was inhibited by 38% by TTX. When tested together, l-NAME in the presence of TTX or TTX in the presence of l-NAME had no further effect on the amplitude or frequency of spontaneous contractions, and the NO production was inhibited. These findings suggest that basal NO consists of TTX-sensitive and TTX-resistant components. The TTX-sensitive NO has an inhibitory effect on spontaneous contractions; the role of TTX-resistant NO is unknown.

Adenosine receptor-mediated relaxation of rabbit airway smooth muscle: a role for nitric oxide

1997 ◽  
Vol 273 (3) ◽  
pp. L581-L587 ◽  
Author(s):  
S. Ali ◽  
W. J. Metzger ◽  
H. A. Olanrewaju ◽  
S. J. Mustafa
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Epithelial Cells ◽  
Airway Smooth Muscle ◽  
Adenosine Receptor ◽  
Inhibitory Effect ◽  
No Production ◽  
Relaxant Effect ◽  
Adenosine Receptor Agonists ◽  
Cgs 21680

In this study, we investigated the relaxant effect of adenosine receptor agonists on KCl-precontracted airway smooth muscle from rabbits and characterized the type of receptor involved in bronchorelaxation in the presence and absence of epithelium. We further defined the role of epithelium-derived relaxing factor, i.e., nitric oxide (NO), on these responses. In both epithelium-intact and -denuded tertiary airway rings from rabbits, the adenosine receptor agonists 2-[p-(2-carboxyethyl)]phenylethylamino-5-N'-ethylcarboxamidoadenos ine (CGS-21680), 5'-(N-ethyl-carboxamido)adenosine (NECA), 2-chloroadenosine (CAD), and (-)-N6-(2-phenylisopropyl)adenosine (R-PIA) relaxed airway smooth muscle with a potency order of CGS-21680 > NECA > CAD > R-PIA. A 98.5, 89.7, 73.2, and 64.7% relaxation was observed at 10(-5) M by CGS-21680, NECA, CAD, and R-PIA in the epithelium-intact bronchial rings, respectively. The 50% maximum effective concentration (EC50; x 10(-7) M) values for CGS-21680, NECA, CAD, and R-PIA were 2, 4, 9, and 80, respectively. Denuded rings, however, showed much less relaxant responses to various adenosine agonists compared with epithelium-intact rings. The adenosine receptor antagonist 8-(sulfophenyl)theophylline significantly attenuated the relaxant responses to all the agonists in the epithelium-intact and -denuded rings. The epithelium-dependent relaxant effect of the agonists in airway rings was inhibited by NG-monomethyl-L-arginine (L-NMMA; 30 microM). The EC50 (x 10(-6) M) values for CGS-21680, NECA, CAD, and R-PIA in the presence of inhibitor were 5.5, 8, 30, and 200, respectively. The L-NMMA produced an insignificant inhibitory effect in the epithelium-denuded rings. L-Arginine but not D-arginine (100 microM) reversed the inhibitory effect of L-NMMA on adenosine agonist-induced relaxation. In primary epithelial cells in culture, CGS-21680 (10(-5) M) induced a fourfold increase in NO production over the control. The CGS-21680-induced NO production in epithelial cells was significantly inhibited by NG-nitro-L-arginine methyl ester (L-NAME). Moreover, L-arginine reversed the inhibitory effect of L-NAME in the epithelial cells. The data suggest that adenosine relaxes rabbit airway smooth muscle through an A2 adenosine receptor and the epithelium serves as a source of NO.

Interactive effects of PTH and mechanical stress on nitric oxide and PGE2 production by primary mouse osteoblastic cells

2003 ◽  
Vol 285 (3) ◽  
pp. E608-E613 ◽  
Author(s):  
Astrid D. Bakker ◽  
Manon Joldersma ◽  
Jenneke Klein-Nulend ◽  
Elisabeth H. Burger
Keyword(s):  
Nitric Oxide ◽  
Fluid Flow ◽  
Bone Formation ◽  
Mechanical Stress ◽  
Bone Cells ◽  
Osteoblastic Cells ◽  
Prostaglandin E ◽  
No Production ◽  
Simultaneous Application ◽  
Primary Mouse

Parathyroid hormone (PTH) and mechanical stress both stimulate bone formation but have opposite effects on bone resorption. PTH increased loading-induced bone formation in a rat model, suggesting that there is an interaction of these stimuli, possibly at the cellular level. To investigate whether PTH can modulate mechanotransduction by bone cells, we examined the effect of 10-9 M human PTH-(1-34) on fluid flow-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production by primary mouse osteoblastic cells in vitro. Mechanical stress applied by means of a pulsating fluid flow (PFF; 0.6 ± 0.3 Pa at 5 Hz) stimulated both NO and PGE2 production twofold. In the absence of stress, PTH also caused a twofold increase in PGE2 production, but NO release was not affected and remained low. Simultaneous application of PFF and PTH nullified the stimulating effect of PFF on NO production, whereas PGE2 production was again stimulated only twofold. Treatment with PTH alone reduced NO synthase (NOS) enzyme activity to undetectable levels. We speculate that PTH prevents stress-induced NO production via the inhibition of NOS, which will also inhibit the NO-mediated upregulation of PGE2 by stress, leaving only the NO-independent PGE2 upregulation by PTH. These results suggest that mechanical loading and PTH interact at the level of mechanotransduction.

scholarly journals In vitro and in vivo anti-inflammatory activities of a sterol-enriched fraction from freshwater green alga, Spirogyra sp.

2020 ◽  
Vol 23 (1) ◽  
Author(s):  
Lei Wang ◽  
You-Jin Jeon ◽  
Jae-Il Kim
Keyword(s):  
Nitric Oxide ◽  
Green Alga ◽  
Raw 264.7 Cells ◽  
Ros Generation ◽  
Prostaglandin E ◽  
No Production ◽  
Raw 264.7 ◽  
Anti Inflammatory

Abstract Background Inflammation plays a crucial role in the pathogenesis of many diseases such as arthritis and atherosclerosis. In the present study, we evaluated anti-inflammatory activity of sterol-rich fraction prepared from Spirogyra sp., a freshwater green alga, in an effort to find bioactive extracts derived from natural sources. Methods The sterol content of ethanol extract of Spirogyra sp. (SPE) was enriched by fractionation with hexane (SPEH), resulting 6.7 times higher than SPE. Using this fraction, the in vitro and in vivo anti-inflammatory activities were evaluated in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells and zebrafish. Results SPEH effectively and dose-dependently decreased the production of nitric oxide (NO) and prostaglandin E2 (PGE2). SPEH suppressed the production of pro-inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β through downregulating nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW 264.7 cells without cytotoxicity. The in vivo test results indicated that SPEH significantly and dose-dependently reduced reactive oxygen species (ROS) generation, cell death, and NO production in LPS-stimulated zebrafish. Conclusions These results demonstrate that SPEH possesses strong in vitro and in vivo anti-inflammatory activities and has the potential to be used as healthcare or pharmaceutical material for the treatment of inflammatory diseases.

scholarly journals Smoking-Induced Inhibition of Number and Activity of Endothelial Progenitor Cells and Nitric Oxide in Males Were Reversed by Estradiol in Premenopausal Females

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yijia Shao ◽  
Liang Luo ◽  
Zi Ren ◽  
Jiayi Guo ◽  
Xingxing Xiao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cigarette Smoking ◽  
Premenopausal Women ◽  
Cross Sectional Study ◽  
Favorable Effect ◽  
No Production ◽  
Vascular Protection ◽  
Cross Sectional ◽  
And Function ◽  
Flow Mediated Vasodilation

Objectives. The number and activity of circulating EPCs were enhanced in premenopausal women contrast to postmenopausal females and age-matched males. Here, we investigated whether this favorable effect exists in premenopausal women and age-matched men with cigarette smoking. Methods. In a cross-sectional study, the number and activity of circulating EPCs and nitric oxide production (NO) as well as flow-mediated vasodilation (FMD) in both premenopausal women and age-matched men with or without cigarette smoking were studied. Results. Compared with age-matched men with or without smoking, the number and function of circulating EPCs as well as NO level in premenopausal women were obviously higher than that in the former and not affected by smoking. The number and function of circulating EPCs as well as NO level in male smokers were shown to be the most strongly inhibited. Furthermore, there was significant correlation between EPC number and activity, plasma NO level, and NO secretion by EPCs and FMD. Conclusions. Estradiol was deemed to play an important role in enhancing the number and activity of EPCs and NO production in premenopausal women even when affected by smoking, which may be the important mechanisms underlying vascular protection of estradiol in premenopausal women, but not in age-matched men.

scholarly journals The role of nitric oxide on matrix metalloproteinase 2 (MMP2) and MMP9 in placenta and fetus from diabetic rats

Reproduction ◽  
2007 ◽  
Vol 134 (4) ◽  
pp. 605-613 ◽  
Author(s):  
M C Pustovrh ◽  
A Jawerbaum ◽  
V White ◽  
E Capobianco ◽  
R Higa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Structural Changes ◽  
Diabetic Rats ◽  
Matrix Metalloproteinase 2 ◽  
No Donor ◽  
Diaphorase Activity ◽  
Nos Inhibitor ◽  
And Function ◽  
Fetal Organs

Matrix metalloproteinases (MMPs) play an important role in tissue remodeling that accompanies the rapid growth, differentiation, and structural changes of the placenta and several fetal organs. In the present study, we investigated whether the diabetic maternal environment may alter the regulatory homeostasis exerted by nitric oxide (NO) on MMPs activity in the feto-placental unit from rats at midgestation. We found that NADPH-diaphorase activity, which reflects the distribution and activity of NO synthases (NOS), was increased in both placenta and fetuses from diabetic rats when compared with controls. In addition, while a NO donor enhanced MMP2 and MMP9 activities, a NOS inhibitor reduced these activities in the maternal side of the placenta from control rats. This regulatory effect of NO was only observed on MMP9 in the diabetic group. On the other hand, the NO donor did not modify MMP2 and MMP9 activities, while the NOS inhibitor reduced MMP9 activity in the fetal side of both control and diabetic placentas. In the fetuses, MMP2 was enhanced by the NO donor and reduced by the NO inhibitor in both fetuses from control and diabetic rats. Overall, this study demonstrates that NO is able to modulate the activation of MMPs in the feto-placental unit, and provides supportive evidence that increased NOS activity leads to NO overproduction in the feto-placental unit from diabetic rats, an alteration closely related to the observed MMPs dysregulation that may have profound implications in the formation and function of the placenta and the fetal organs.

Nitric oxide augments fetal pulmonary artery endothelial cell angiogenesis in vitro

2006 ◽  
Vol 290 (6) ◽  
pp. L1111-L1116 ◽  
Author(s):  
Vivek Balasubramaniam ◽  
Anne M. Maxey ◽  
Brian W. Fouty ◽  
Steven H. Abman
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Oxygen Tension ◽  
Growth And Development ◽  
Tube Formation ◽  
No Production ◽  
Low Oxygen ◽  
Low Oxygen Tension ◽  
And Function ◽  
Pulmonary Artery Endothelial Cell

Growth and development of the lung normally occur in the low oxygen environment of the fetus. The role of this low oxygen environment on fetal lung endothelial cell growth and function is unknown. We hypothesized that low oxygen tension during fetal life enhances pulmonary artery endothelial cell (PAEC) growth and function and that nitric oxide (NO) production modulates fetal PAEC responses to low oxygen tension. To test this hypothesis, we compared the effects of fetal (3%) and room air (RA) oxygen tension on fetal PAEC growth, proliferation, tube formation, and migration in the presence and absence of the NO synthase (NOS) inhibitor Nω-nitro-l-arginine (LNA), and an NO donor, S-nitroso- N-acetylpenicillamine (SNAP). Compared with fetal PAEC grown in RA, 3% O2 increased tube formation by over twofold ( P < 0.01). LNA treatment reduced tube formation in 3% O2 but had no affect on tube formation in RA. Treatment with SNAP increased tube formation during RA exposure to levels observed in 3% O2. Exposure to 3% O2 for 48 h attenuated cell number (by 56%), and treatment with LNA reduced PAEC growth by 44% in both RA and 3% O2. We conclude that low oxygen tension enhances fetal PAEC tube formation and that NO is essential for normal PAEC growth, migration, and tube formation. Furthermore, we conclude that in fetal cells exposed to the relative hyperoxia of RA, 21% O2, NO overcomes the inhibitory effects of the increased oxygen, allowing normal PAEC angiogenesis and branching. We speculate that NO production maintains intrauterine lung vascular growth and development during exposure to low O2 in the normal fetus. We further speculate that NO is essential for pulmonary angiogenesis in fetal animal exposed to increased oxygen tension of RA and that impaired endothelial NO production may contribute to the abnormalities of angiogenesis see in infants with bronchopulmonary dysplasia.

Hyperglycemia impairs glucose and insulin regulation of nitric oxide production in glucose-inhibited neurons in the ventromedial hypothalamus

2007 ◽  
Vol 293 (2) ◽  
pp. R592-R600 ◽  
Author(s):  
Debra D. Canabal ◽  
Joseph G. Potian ◽  
Ricardo G. Duran ◽  
Joseph J. McArdle ◽  
Vanessa H. Routh
Keyword(s):  
Nitric Oxide ◽  
Membrane Potential ◽  
Insulin Signaling ◽  
Mammalian Target Of Rapamycin ◽  
Ventromedial Hypothalamus ◽  
Diabetic Rats ◽  
No Production ◽  
Insulin Regulation ◽  
Obesity And Diabetes ◽  
Extracellular Glucose

Physiological changes in extracellular glucose, insulin, and leptin regulate glucose-excited (GE) and glucose-inhibited (GI) neurons in the ventromedial hypothalamus (VMH). Nitric oxide (NO) signaling, which is involved in the regulation of food intake and insulin signaling, is altered in obesity and diabetes. We previously showed that glucose and leptin inhibit NO production via the AMP-activated protein kinase (AMPK) pathway, while insulin stimulates NO production via the phosphatidylinositol-3-OH kinase (PI3K) pathway in VMH GI neurons. Hyperglycemia-induced inhibition of AMPK reduces PI3K signaling by activating the mammalian target of rapamycin (mTOR). We hypothesize that hyperglycemia impairs glucose and insulin-regulated NO production in VMH GI neurons. This hypothesis was tested in VMH neurons cultured in hyperglycemic conditions or from streptozotocin-induced type 1 diabetic rats using NO- and membrane potential-sensitive dyes. Neither decreased extracellular glucose from 2.5 to 0.5 mM, nor 5 nM insulin increased NO production in VMH neurons in either experimental condition. Glucose- and insulin-regulated NO production was restored in the presence of the AMPK activator, 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside or the mTOR inhibitor rapamycin. Finally, decreased glucose and insulin did not alter membrane potential in VMH neurons cultured in hyperglycemic conditions or from streptozotocin-induced rats. These data suggest that hyperglycemia impairs glucose and insulin regulation of NO production through AMPK inhibition. Furthermore, glucose and insulin signaling pathways interact via the mTOR pathway.

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