No arguments for increased endothelial nitric oxide synthase activity in migraine based on peripheral biomarkers

Cephalalgia ◽  
2010 ◽  
Vol 30 (11) ◽  
pp. 1354-1365 ◽  
Author(s):  
Bart J Van der Schueren ◽  
Frederik H Verbrugge ◽  
René Verbesselt ◽  
Anne Van Hecken ◽  
Marleen Depré ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Healthy Subjects ◽  
No Synthase ◽  
Saline Infusion ◽  
Controlled Study ◽  
Loading Dose ◽  
Arginine Infusion ◽  
Exhaled No ◽  
Oxide Synthase

Objectives: To assess whether migraine patients display a chronic nitric oxide synthase (NOS) hyperactivity by comparing the nitric oxide (NO) production before and following a loading dose of L-arginine between migraine patients (interictally) and matched healthy control subjects. In addition, we evaluated whether a loading dose of L-arginine triggers an acute migraine headache in migraineurs. Subjects and methods: Twenty healthy subjects and 20 migraine patients participated in a 2-period, randomised, double-blind, placebo-controlled study. Each subject received a 30-min infusion, by peripheral vein, of 30 g L-arginine hydrochloride or placebo (i.e. an equal volume of 0.9% saline solution). Meanwhile, biomarkers associated with the L-arginine–NO pathway (i.e. exhaled NO/nasal NO), plasma citrulline and urinary excretion of nitrite/nitrate and cGMP were assessed before and for 6 h following the start of the infusion. Results: At baseline, exhaled NO and nasal NO were higher in migraineurs compared to healthy subjects (mean ± 95% confidence interval): 15.9 (8.8, 23.0) parts per billion (ppb) versus 10.8 (7.0, 14.5) ppb for exhaled NO ( P = 0.04) and 76.3 (61.2, 91.4) versus 61.6 (51.2, 72.0) ppb for nasal NO ( P = 0.03), respectively. The AUC0–6 in ppb for exhaled NO and nasal NO following L-arginine or saline infusion did not differ between both groups. The increase in L-citrulline, following L-arginine infusion, was smaller in migraine patients (15 (13, 18) µmol/l) compared to healthy volunteers (19 (16, 23) µmol/l; P = 0.046). In healthy subjects, both nitrate and cGMP excretion were higher following L-arginine compared to placebo infusion: 132.63 (100.24, 165.02) versus 92.07 (66.33, 117.82) µmol/mmol creatinine for nitrate ( P = 0.014) and 50.53 (42.19, 58.87) versus 39.64 (33.94, 45.34) nmol/mmol creatinine for cGMP ( P = 0.0003), respectively. In migraineurs, excretion of these biomarkers was comparable following L-arginine or saline infusion. Conclusions: The results of the present study do not support the idea of a generalised increase in NO synthase activity in migraine patients outside of a migraine attack. The smaller increase in plasma L-citrulline, urinary nitrate and cGMP excretion following L-arginine infusion in migraine patients might indicate dysfunction of endothelial NO synthase.

scholarly journals Associations between Nitric Oxide Synthase Genes and Exhaled NO-Related Phenotypes according to Asthma Status

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e36672 ◽  
Author(s):  
Emmanuelle Bouzigon ◽  
Florent Monier ◽  
Mekki Boussaha ◽  
Nicole Le Moual ◽  
Hélène Huyvaert ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Exhaled No ◽  
Asthma Status ◽  
Oxide Synthase

Characterization and localization of endothelial nitric oxide synthase using specific monoclonal antibodies

1993 ◽  
Vol 265 (5) ◽  
pp. C1379-C1387 ◽  
Author(s):  
J. S. Pollock ◽  
M. Nakane ◽  
L. D. Buttery ◽  
A. Martinez ◽  
D. Springall ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
No Synthase ◽  
Endothelial No Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We have produced specific monoclonal antibodies (MAb) against particulate bovine aortic endothelial nitric oxide synthase. In Western blots, native and cultured bovine aortic endothelial cells as well as cultured bovine microvascular endothelial cells possess immunoreactive NO synthase. In dot blots, MAb H210 and H32 detect 1 ng and 100 pg of purified endothelial NO synthase, respectively. Both antibodies are specific to the endothelial NO synthase and do not cross-react with other known isoforms of NO synthase, namely from the brain, from cytokine/endotoxin-induced macrophages, or from cytokine/endotoxin-induced vascular smooth muscle cells. Immunohistochemical studies demonstrated the specificity of endothelial NO synthase for endothelial cells in various bovine and human tissues. Many types of endothelial cells, macrovascular, microvascular, arterial, and venous were found to possess this specific isoform of NO synthase. Electron microscopy showed the enzyme to be associated with the plasma membrane, membranes of cytoplasmic vesicles, and in the cytoplasm in human umbilical vein endothelial cells. The results demonstrate that particulate endothelial NO synthase is present in a site to act rapidly to produce NO for release into the blood or toward the smooth muscle in many vascular beds.

The effect of nitric oxide synthase 4ab gene polymorphism on vascular endothelial function in healthy subjects

2003 ◽  
Vol 12 (2) ◽  
pp. A55
Author(s):  
Bill Bilsborough ◽  
Daniel J. Green ◽  
Cyril D.S. Mamotte ◽  
Frank M. van Bockxmeer ◽  
Gerry O'Driscoll ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Gene Polymorphism ◽  
Endothelial Function ◽  
Healthy Subjects ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Oxide Synthase

scholarly journals Brain nitric oxide synthase is a haemoprotein

1992 ◽  
Vol 288 (1) ◽  
pp. 15-17 ◽  
Author(s):  
P Klatt ◽  
K Schmidt ◽  
B Mayer
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
No Synthase ◽  
Oxide Synthase ◽  
Brain Nitric Oxide

Brain nitric oxide (NO) synthase showed pyridine haemochrome spectra typical of ferroprotoporphyrin IX-containing enzymes. The haem content of purified NO synthase was in the range 0.7-0.9 mol/mol of 160 kDa subunit. In the presence of CO, NO, KCN and miconazole, the L-citrulline-forming activity of NO synthase was markedly diminished, demonstrating that enzyme-bound haem is involved in enzymic NO synthesis.

scholarly journals Endothelial Nitric Oxide Synthase-Dependent Cerebral Blood Flow Augmentation by L-Arginine After Chronic Statin Treatment

2000 ◽  
Vol 20 (4) ◽  
pp. 709-717 ◽  
Author(s):  
Masaru Yamada ◽  
Zhihong Huang ◽  
Turgay Dalkara ◽  
Matthias Endres ◽  
Ulrich Laufs ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Laser Doppler Flowmetry ◽  
Brain Blood Flow ◽  
Arginine Infusion ◽  
Doppler Flowmetry ◽  
Ischemic Brain ◽  
Oxide Synthase

Nitric oxide, a product of nitric oxide synthase activity, relaxes vascular smooth muscle and elevates brain blood flow. We evaluated the importance of eNOS to cerebral blood flow augmentation after L-arginine infusion and increases in flow after eNOS upregulation in SV-129 mice. Blood flow was measured by laser-Doppler flowmetry before and after L-arginine infusion (450 mg/kg during a 15-minute period) or measured by 14C-iodoamphetamine indicator fractionation or 14C-iodoantipyrine tissue equilibration techniques. rCBF increased by 26% (laser Doppler flowmetry) after L-arginine infusion but did not change in mutant mice deficient in eNOS expression. After eNOS upregulation by chronic simvastatin treatment (2 mg/kg subcutaneously, daily for 14 days), L-arginine amplified and sustained the hyperemia (38%) and increased absolute brain blood flow from 86 ± 7 to 119 ± 10 mL/100 g per minute. Furthermore, pretreatment with simvastatin enhanced blood flow within ischemic brain tissue after middle cerebral artery occlusion. Together, these findings suggest that eNOS activity is critical for blood flow augmentation during acute L-arginine infusion, and chronic eNOS upregulation combined with L-arginine administration provides a novel strategy to elevate cerebral blood flow in the normal and ischemic brain.

Evidence that nitric oxide synthase is involved in progesterone-induced acrosomal exocytosis in mouse spermatozoa

1997 ◽  
Vol 9 (4) ◽  
pp. 433 ◽  
Author(s):  
María Beléen Herrero ◽  
J. Marcelo Viggiano ◽  
Silvina Pérez Martínez ◽  
Martha F. de Gimeno
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
No Synthase ◽  
Nitric Oxide Donor ◽  
Mouse Sperm ◽  
Acrosomal Exocytosis ◽  
Oxide Synthase ◽  
Spermine Nonoate

In a recent work, we detected nitric oxide synthase (NO synthase) in the acrosome and tail of mouse and human spermatozoa by an immunofluorescence technique. Also, NO-synthase inhibitors added during sperm capacitationin vitro reduced the percentage of oocytes fertilized in vitro, suggesting a role for NO synthase in sperm function. Therefore, in the present study the effect of three NO-synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME), NG-nitro-D-arginine methyl ester (D-NAME) and L-NG-nitro-arginine (NO2-arg), and of a nitric oxide donor, spermine-NONOate, on the progesterone-induced acrosome reaction of mouse sperm was examined. NO-synthase inhibitors were added at 0, 60 or 90 min during capacitation; at 120 min, mouse epididymal spermatozoa were exposed to 15 µM progesterone for another 15 min. In another set of experiments, different concentrations of spermine-NONOate were added to capacitated spermatozoa for 15 min; in these experiments, progesterone was not included. NO2-arg and L-NAME blocked progesterone-induced exocytosis regardless of the time at which these inhibitors were added. Moreover, D-NAME did not inhibit exocytosis. In contrast, spermine-NONOate stimulated the acrosomal exocytosis in vitro directly. These results provide evidence that mouse sperm NO synthase participates in the progesterone-induced acrosome reactionin vitro and that nitric oxide induces this event.

Nitric Oxide Synthase Is Deficient in the Aganglionic Colon of Patients With Hirschsprung's Disease

PEDIATRICS ◽  
1994 ◽  
Vol 93 (4) ◽  
pp. 647-651
Author(s):  
John F. Bealer ◽  
Eileen S. Natuzzi ◽  
Cori Buscher ◽  
Alan W. Flake ◽  
N. Scott Adzick ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Enzyme Activity ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase ◽  
Nicotinamide Adenine Dinucleotide ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
No Synthase ◽  
Oxide Synthase

Objectives. The cause of Hirschsprung's disease is unknown but defects in nonadrenergic, noncholinergic innervation could prevent relaxation of aganglionic colon in patients with this disease. Nonadrenergic, noncholinergic nerves induce relaxation by using nitric oxide synthase to produce the smooth muscle relaxant nitric oxide (NO). In this study we asked whether aganglionic colon in patients with Hirschsprung's disease is deficient in NO synthase-containing nerves. Methodology. Using the tetrazolium blue dye method of demonstrating nicotinamide adenine dinucleotide phosphate-diaphorase enzymes, we examined eight colon specimens (four aganglionic and four ganglionic) from patients with Hirschsprung's disease for the presence of NO synthase. We further quantified NO synthase enzyme activity in these eight specimens by using the [3H]arginine-to-[3H]citrulline conversion assay. Results. The nicotinamide adenine dinucleotide phosphate-diaphorase staining showed that aganglionic colon contained less NO synthase than ganglionic colon. This NO synthase deficiency was located primarily in the nerves of the circular muscle layer of the colon. In addition, there was a striking difference in the NO synthase enzyme activity between aganglionic and ganglionic colon as measured by the [3H]arginine-to-[3H]citrulline conversion assay. Total NO synthase activity, as measured by this assay, was found to be less in aganglionic than in ganglionic colon. When the total activity was divided into its four known isoforms, aganglionic colon was noted to be striking deficient in the isoform derived primarily from nerves. Conclusion. We conclude that aganglionic colon is deficient in NO synthase-containing nerves. This deficiency could prevent smooth muscle relaxation in the aganglionic colon of patients with Hirschsprung's disease.

scholarly journals Identification of the 4-amino analogue of tetrahydrobiopterin as a dihydropteridine reductase inhibitor and a potent pteridine antagonist of rat neuronal nitric oxide synthase

1996 ◽  
Vol 320 (1) ◽  
pp. 193-196 ◽  
Author(s):  
Ernst R. WERNER ◽  
Eva PITTERS ◽  
Kurt SCHMIDT ◽  
Helmut WACHTER ◽  
Gabriele WERNER-FELMAYER ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Reductase Inhibitor ◽  
Neuronal Nitric Oxide Synthase ◽  
Redox Cycling ◽  
No Synthase ◽  
Dihydropteridine Reductase ◽  
Basal Activity ◽  
Potent Antagonist ◽  
Oxide Synthase

The binding of tetrahydropteridines with 6-di- and trihydroxypropyl side chains to recombinant rat neuronal nitric oxide (NO) synthase (EC 1.14.13.39) was determined by competition with 6R-[3´-3H]-5,6,7,8-tetrahydro-L-erythro-biopterin (6R-[3´-3H]H4biopterin). Although all but one of the derivatives exhibited only poor affinities (Ki 50 µM), the 4-amino analogue of 6R-H4biopterin was a potent antagonist of 6R-H4biopterin binding (Ki 13.2 nM). The 4-amino analogue of 6R-H4 biopterin inhibited NO synthase stimulation by the natural cofactor 6R-H4biopterin with an IC50 of 1 µM without affecting the basal activity observed in the absence of added 6R-H4biopterin. Because the 4-amino analogue of 6R-H4biopterin also inhibited dihydropteridine reductase (EC 1.6.99.7; IC50 20 µM), our results support the hypothesis that redox cycling of H4biopterin might be required for the NO synthase reaction.

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