scholarly journals Analysis of NOS Gene Polymorphisms in Relation to Cluster Headache and Predisposing Factors in Sweden

2020 ◽  
Vol 11 (1) ◽  
pp. 34
Author(s):  
Caroline Ran ◽  
Julia M. Michalska ◽  
Carmen Fourier ◽  
Christina Sjöstrand ◽  
Elisabet Waldenlind ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cluster Headache ◽  
Genetic Variants ◽  
Potential Candidate ◽  
Nitric Oxide Signaling ◽  
Minor Alleles ◽  
Oxide Synthase ◽  
Trigeminal Reflex ◽  
Inducible Nos ◽  
Nos Gene

Cluster headache is characterized by activation of the autonomic-trigeminal reflex. Nitric oxide can trigger headaches in patients, and nitric oxide signaling is known to be affected in cluster headache. Based on the hypothesis of nitric oxide being involved in cluster headache pathophysiology we investigated nitric oxide synthases as potential candidate genes for cluster headache. We analyzed eight variants in the three forms of nitric oxide synthase (NOS) genes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS), and tested for association with cluster headache. Swedish cluster headache patients (n = 542) and controls (n = 581) were genotyped using TaqMan® assays on an Applied Biosystems 7500 qPCR cycler. This is the largest performed genetic study on NOS involvement in cluster headache so far. We found an association between cluster headache and one iNOS haplotype consisting of the minor alleles of rs2297518 and rs2779249 (p = 0.022). In addition, one of the analyzed nNOS variants, rs2682826, was associated with reported triptan use (p = 0.039). Our data suggest that genetic variants in NOS genes do not have a strong influence on cluster headache pathophysiology, but that certain combinations of genetic variants in NOS genes may influence the risk of developing the disorder or triptan use.

scholarly journals Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying

2002 ◽  
Vol 283 (6) ◽  
pp. G1360-G1367 ◽  
Author(s):  
Sara Calatayud ◽  
Eugenia García-Zaragozá ◽  
Carlos Hernández ◽  
Elsa Quintana ◽  
Vicente Felipo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Gastric Emptying ◽  
Methyl Ester ◽  
Intraperitoneal Injection ◽  
Delayed Gastric Emptying ◽  
Single Intraperitoneal Injection ◽  
Inos Inhibitor ◽  
Oxide Synthase ◽  
Experimental Group ◽  
Inducible Nos

A single intraperitoneal injection of endotoxin (40 μg/kg) significantly delayed gastric emptying of a solid nutrient meal. Blockade of nitric oxide synthase (NOS) with 30 mg/kg ip N G-nitro-l-arginine methyl ester or 20 mg/kg ip 7-nitroindazole [neuronal NOS (nNOS) inhibitor] significantly delayed gastric emptying in control animals but failed to modify gastric emptying in endotoxin-treated rats. Administration of 2.5, 5, and 10 mg/kg ip N 6-iminoethyl-l-lysine [inducible NOS (iNOS) inhibitor] had no effect in either experimental group. Indomethacin (5 mg/kg sc), NS-398 (cyclooxygenase-2 inhibitor; 10 mg/kg ip), and dexamethasone (10 mg/kg sc) but not quinacrine (20 mg/kg ip) significantly prevented delay in gastric emptying induced by endotoxin but failed to modify gastric emptying in vehicle-treated animals. Ca2+-dependent NOS activity in the antrum pylorus of the stomach was diminished by endotoxin, whereas Ca2+-independent NOS activity was not changed. In addition, decreased nNOS mRNA and protein were observed in the antrum pylorus of endotoxin-treated rats. Our results suggest that downregulation of nNOS in the antrum pylorus of the stomach and synthesis of prostaglandins mediate the delay in gastric emptying of a solid nutrient meal induced by endotoxin.

scholarly journals Modulation of Opioid Actions by Nitric Oxide Signaling

2009 ◽  
Vol 110 (1) ◽  
pp. 166-181 ◽  
Author(s):  
Noboru Toda ◽  
Shiroh Kishioka ◽  
Yoshio Hatano ◽  
Hiroshi Toda ◽  
David S. Warner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Glial Cells ◽  
Withdrawal Syndrome ◽  
Therapeutic Agents ◽  
Nitric Oxide Signaling ◽  
Endogenous Nitric Oxide ◽  
Oxide Synthase ◽  
New Strategies

Nitric oxide (NO) plays pivotal roles in controlling physiological functions, participates in pathophysiological intervention, and is involved in mechanisms underlying beneficial or untoward actions of therapeutic agents. Endogenous nitric oxide is formed by three isoforms of nitric oxide synthase: endothelial, neurogenic and inducible. The former two are constitutively present mainly in the endothelium and nervous system, respectively, and the latter one is induced by lipopolysaccharides or cytokines mainly in mitochondria and glial cells. Constitutively formed nitric oxide modulates the actions of morphine and related analgesics by either enhancing or reducing antinociception. Tolerance to and dependence on morphine or its withdrawal syndrome are likely prevented by nitric oxide synthase inhibition. Information concerning modulation of morphine actions by nitric oxide is undoubtedly useful in establishing new strategies for efficient antinociceptive treatment and for minimizing noxious and unintended reactions.

Nitric oxide, ischaemia and brain inflammation

2007 ◽  
Vol 35 (5) ◽  
pp. 1133-1137 ◽  
Author(s):  
S. Murphy ◽  
C.L. Gibson
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cerebral Ischaemia ◽  
Brain Inflammation ◽  
Experimental Stroke ◽  
Nitric Oxide Donors ◽  
Nos Inhibitors ◽  
Oxide Synthase ◽  
Inducible Nos

Cerebral ischaemia results in the activation of three isoforms of NOS (nitric oxide synthase) that contribute to the development of and recovery from stroke pathology. This review discusses, in particular, the role of the transcriptionally activated NOS-2 (inducible NOS) isoform and summarizes the outcomes of experimental stroke studies with regard to the therapeutic utility of nitric oxide donors and NOS inhibitors.

Timing of Administration of Dexamethasone or the Nitric Oxide Synthase Inhibitor, Nitro-l-Arginine Methyl Ester, is Critical for Effective Treatment of Ischaemia-Reperfusion Injury to Rat Skeletal Muscle

1997 ◽  
Vol 93 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Baimeng Zhang ◽  
Kenneth R. Knight ◽  
Bruce Dowsing ◽  
Elizabeth Guida ◽  
Long H. Phan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Reperfusion Injury ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Nos Inhibitors ◽  
Oxide Synthase ◽  
Inducible Nos

1. The effects of the nitric oxide synthase (NOS) inhibitors, NG-nitro-l-arginine-methyl ester (l-NAME), nitroiminoethyl-l-ornithine and S-methylisothiourea on skeletal muscle survival following 2 h of tourniquet ischaemia and 24 h of reperfusion were compared with those of the antiinflammatory steroid, dexamethasone. 2. Administration of each of the NOS inhibitors or dexamethasone 30 min before reperfusion reduced the degree of skeletal muscle necrosis 24 h after reperfusion. 3. The influence of timing of drug administration was investigated. l-NAME administered 30 min before reperfusion, at 3 h after reperfusion, but not thereafter, significantly improved muscle survival compared with saline-treated controls. Dexamethasone administered 30 min before, or at 3 or 8 h after reperfusion, but not at 16 h, significantly improved muscle survival, but neither agent had protective effects when administered before ischaemia. 4. After 8 h of reperfusion of ischaemic skeletal muscle, cell-free homogenates contained Ca2+-independent (inducible) NOS activity which was reduced in dexamethasone-treated (2.5 mg/kg) rats. Furthermore, inducible NOS mRNA levels, as detected by reverse transcriptase-PCR, were increased after 8 h of reperfusion in saline, but not in dexamethasone-treated rats. 5. These data suggest a significant deleterious effect of endogenous NO which may be restricted to the first 3 h of the reperfusion phase of ischaemia-reperfusion injury, and raise the possibility of effective treatment of incipient reperfusion injury, even after several hours of reperfusion.

Inducible nitric oxide synthase in the epithelial epididymal cells of the rat

1997 ◽  
Vol 9 (8) ◽  
pp. 789 ◽  
Author(s):  
Barbara Wiszniewska ◽  
Rafal Kurzawa ◽  
Andrzej Ciechanowicz ◽  
Boguslaw Machalinski
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Epithelial Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Cultured Cells ◽  
No Production ◽  
Nitrite Production ◽  
Oxide Synthase ◽  
Inducible Nos ◽  
Inducible Nitric Oxide

The expression of mRNA for inducible nitric oxide synthase (iNOS) in rat epithelial cells of epididymis was investigated with reverse transcription followed by polymerase chain reaction. Immunocytochemical reaction for iNOS was performed to confirm the enzyme’ s localization in the epididymal epithelium. Additionally, an indirect spectrophotometric method for nitric oxide (NO) determination was applied for measurement of nitrite production by cultured epididymal epithelial cells. Inducible NOS mRNA was detected in freshly isolated epithelial cells, in cultured cells without stimulation as well as in cultured cells after stimulation by lipopolysaccharide and interferon-gamma. Inducible NOS immunoreactivity was observed in the apical part of epithelial cells of epididymal sections and in the cytoplasm of cells in culture. Release of nitrite was observedin vitro in both the unstimulated and stimulated cells of caput (1·44 ± 0·94 v. 4·37 ± 2·42 µM) and cauda (0·69 ± 1·21 v. 5·21 ± 2·76 µM) epididymis (P < 0·001). To the best of our knowledge, this is the first study to demonstrate iNOS in the epididymal epithelial cells of the rat. Nitric oxide released by epididymal epithelial cells may act on cells and tissues located nearby. The results may help explain epididymal function: sperm storage, passage and maturation. Excessive epididymal NO production may also play a role in the inflammatory infertility of the male. Extra keyword: iNOS

Myogenic NOS and endogenous NO production are defective in colon from dystrophic (mdx) mice

2001 ◽  
Vol 281 (5) ◽  
pp. G1264-G1270 ◽  
Author(s):  
Flavia Mulè ◽  
Maria Giuliana Vannucchi ◽  
Letizia Corsani ◽  
Rosa Serio ◽  
Maria Simonetta Faussone-Pellegrini
Keyword(s):  
Nitric Oxide ◽  
Intraluminal Pressure ◽  
Mdx Mice ◽  
No Production ◽  
Free Solution ◽  
Mouse Colon ◽  
Voltage Dependent ◽  
Oxide Synthase ◽  
Nos Isoforms ◽  
Inducible Nos

The aim of the present study was to evaluate whether alterations in the distribution and/or function of nitric oxide synthase (NOS) could be involved in the development of the spontaneous mechanical tone observed in colon from dystrophic ( mdx) mice. By recording the intraluminal pressure of isolated colon from normal mice, we showed that N ω-nitro- l-arginine methyl ester (l-NAME) increased the tone, even in the presence of tetrodotoxin. The effect was prevented by l-arginine, nifedipine, or Ca2+-free solution. In colon from mdx mice, l-NAME was ineffective. Immunohistochemistry revealed that the presence and distribution of neuronal (nNOS), endothelial, and inducible NOS isoforms in smooth muscle cells and neurons of colon from mdx mice were the same as in controls. However, the expression of myogenic nNOS was markedly reduced in mdx mice. We conclude that there is a myogenic NOS in mouse colon that can tonically produce nitric oxide to limit influx of Ca2+ through L-type voltage-dependent channels and modulate the mechanical tone. This mechanism appears to be defective in mdx mice.

scholarly journals Relaxation Effect of Patchouli Alcohol in Rat Corpus Cavernous and Its Underlying Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fangjun Chen ◽  
Yifei Xu ◽  
Jing Wang ◽  
Xufeng Yang ◽  
Hongying Cao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Soluble Guanylate Cyclase ◽  
Corpus Cavernosum ◽  
Relaxation Effect ◽  
Calcium Antagonism ◽  
Nitric Oxide Signaling ◽  
Patchouli Alcohol ◽  
Cox Inhibitor ◽  
Oxide Synthase

In this study, we investigated the relaxation effect and mechanisms of patchouli alcohol (PA) on rat corpus cavernosum. Corpus cavernosum strips were used in organ baths for isometric tension studies. The results showed that PA demonstrated concentration-dependent relaxation effect on rat corpus cavernosum. The relaxant response to PA was not influenced by tetrodotoxin and atropine while it was significantly inhibited by removal of endothelium. L-NG-nitroarginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor) significantly inhibited relaxation response to PA, whereas indomethacin (COX inhibitor) had no effect on PA-induced relaxation. The treatment of endothelium-deprived corpus cavernosum with several potassium channel blockers including tetraethylammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide had no effect on PA-induced relaxation. Endothelium-deprived corpus cavernosal contractions induced by cumulative addition of Ca2+ to high KCl solution without CaCl2 were significantly inhibited by PA. Also, PA improved relaxant capacity of sildenafil in rat corpus cavernosum. In addition, the perfusion with PA significantly increased the levels of cGMP and expression of mRNA and protein of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, intracavernous injection of PA enhanced the rise in intracavernous pressure in rats during cavernosal nerve electric stimulation. In conclusion, PA relaxed the rat corpus cavernosum attributed to both endothelium-dependent and -independent properties. While the former component was mostly involved in nitric oxide signaling pathway, the endothelium-independent mechanism involved in PA-induced relaxation was probably linked to calcium antagonism.

scholarly journals Resting Tension Affects eNOS Activity in a Calcium-Dependent Way in Airways

2007 ◽  
Vol 2007 ◽  
pp. 1-6 ◽  
Author(s):  
Eudoxia Kitsiopoulou ◽  
Apostolia A. Hatziefthimiou ◽  
Konstantinos I. Gourgoulianis ◽  
Paschalis-Adam Molyvdas
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Calcium Concentration ◽  
Kinase Inhibitors ◽  
Calcium Dependent ◽  
Enos Activity ◽  
Resting Tension ◽  
Smooth Muscle Contractions ◽  
Oxide Synthase ◽  
Inducible Nos

The alteration of resting tension (RT) from 0.5 g to 2.5 g increased significantly airway smooth muscle contractions induced by acetylcholine (ACh) in rabbit trachea. The decrease in extracellular calcium concentration[Ca2+]ofrom 2 mM to 0.2 mM reduced ACh-induced contractions only at 2.5 g RT with no effect at 0.5 g RT. The nonselective inhibitor of nitric oxide synthase (NOS),NG-nitro-L-arginine methyl ester (L-NAME) increased ACh-induced contractions at 2.5 g RT. The inhibitor of inducible NOS, S-methylsothiourea or neuronal NOS, 7-nitroindazole had no effect. At 2.5 g RT, the reduction of[Ca2+]ofrom 2 mM to 0.2 mM abolished the effect of L-NAME on ACh-induced contractions. The NO precursor L-arginine or the tyrosine kinase inhibitors erbstatin A and genistein had no effect on ACh-induced contractions obtained at 2.5 g RT. Our results suggest that in airways, RT affects ACh-induced contractions by modulating the activity of epithelial NOS in a calcium-dependent, tyrosine-phosphorylation-independent way.

scholarly journals Enhanced mucosal permeability and nitric oxide synthase activity in jejunum of mast cell deficient mice

Gut ◽  
1997 ◽  
Vol 41 (5) ◽  
pp. 636-641 ◽  
Author(s):  
S Komatsu ◽  
M B Grisham ◽  
J M Russell ◽  
D N Granger
Keyword(s):  
Nitric Oxide ◽  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Cells ◽  
Inhibitory Influence ◽  
Mucosal Permeability ◽  
Nos Inhibitor ◽  
Plasma Nitrate ◽  
Oxide Synthase ◽  
Inducible Nos

Background—Recent reports have described a modulating influence of nitric oxide (NO) on intestinal mucosal permeability and have implicated a role for mast cells in this NO mediated process.Aims—To assess further the contribution of mast cells to the mucosal permeability changes elicited by the NO synthase (NOS) inhibitor NG-nitro-l-arginine methylester (l-NAME), using mast cell deficient (W/WV) and mast cell replete mice (+/+).Methods—Chromium-51 EDTA clearance (from blood to jejunal lumen), jejunal NOS and myeloperoxidase (MPO) activities, and plasma nitrate/nitrite levels were monitored.Results—The increased EDTA clearance elicited by intraluminal l-NAME in W/WV mice (4.4-fold) was significantly greater than the response observed in control (+/+) mice (1.8-fold). The exacerbated response in W/Wv mice was greatly attenuated by pretreatment with either dexamethasone (1.3-fold) or the selective inducible NOS inhibitor, aminoguanidine (1.4-fold), and partially attenuated by the mast cell stabiliser, lodoxamide (2.9-fold). Jejunal inducible NOS activity was significantly higher in W/WV than in +/+ mice, while jejunal MPO was lower in W/WV mice than in +/+ mice, suggesting that the higher inducible NOS in W/WV does not result from the recruitment of inflammatory cells into the gut. The higher inducible NOS activity in the jejunum of W/WV was significantly reduced by dexamethasone treatment.Conclusions—Our results suggest that mast cells normally serve to inhibit inducible NOS activity tonically in the gut and that inhibitors of NOS elicit a larger permeability response when this tonic inhibitory influence is released by mast cell depletion.

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