Effect of a Nitric Oxide Donor (Glyceryl Trinitrate) on Nociceptive Thresholds in Man

Cephalalgia ◽  
1996 ◽  
Vol 16 (3) ◽  
pp. 169-174 ◽  
Author(s):  
LL Thomsen ◽  
J Brennum ◽  
HK Iverson ◽  
J Olesen
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Animal Studies ◽  
Crossover Design ◽  
Nitric Oxide Donor ◽  
Temporal Region ◽  
Double Blind ◽  
No Donor ◽  
Pain Detection ◽  
Nociceptive Input

Several animal studies suggest that nitric oxide (NO) plays a role in central and peripheral modulation of nociception. Glyceryl trinitrate GTN) exerts its physiological actions via donation of NO. The purpose of the present study was to examine the effect of this NO donor on nociceptive thresholds in man. On two different study days separated by at least, week 12 healthy subjects received a staircase infusion of GTN (0.015, 0.25. 1.0, 2.0 mg/kg/min. 20 min each dose) or placebo in a randomized double-blind crossover design. Before the infusion and after 15 min of infusion on each dose, pressure pain detection and tolerance thresholds were determined by pressure a gometry (Somomedic AB, Sweden) in three different anatomic regions (finger, a temporal region with interposed myofascial tissue and a temporal region without interposed myofascial tissue. Relative to placebo, the three higher GTN doses induced a decrease in both detection and tolerance thresholds in the temporal region with interposed myofascial tissue ( p=0.003 detection and p=0.002 tolerance threshold: Friedman). No such changes were observed in the other two stimulated regions. These results could reflect central facilitation of nociception by NO. However, we regard convergence, of nociceptive input from pericranial myofascial tissue and from cephalic blood vessels dilated by NO as a more likely, explanation of our findings.

scholarly journals Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study

2020 ◽  
Vol 34 (8) ◽  
pp. 839-847 ◽  
Author(s):  
Kate Merritt ◽  
Ana Catalan ◽  
Samuel Cowley ◽  
Arsime Demjaha ◽  
Matthew Taylor ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Verbal Memory ◽  
Alternative Hypothesis ◽  
Controlled Trial ◽  
Verbal Learning ◽  
Nitric Oxide Donor ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Double Blind

Background: There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent studies of SNP in patients with psychosis have mixed results, and the drug has to be administered intravenously. Glyceryl trinitrate (GTN) is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. Aims: We explored the safety and potential effects of GTN in unmedicated patients with a first episode of psychosis. Methods: This was a single-centre, randomised, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 × sprays of GTN or placebo for three consecutive days, and were re-assessed on Days 1, 2, 3 and 7. The primary outcome was cognition (Jumping to Conclusions task), secondary outcomes were symptoms (Positive and Negative Syndrome Scale (PANSS)), verbal memory (Hopkins Verbal Learning task), and mood (Bond–Lader Visual Analogue Scales). Results: Nineteen patients were randomised, and 13 participants were included in the analyses. Compared with placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2× more likely under the null hypothesis than the alternative hypothesis, providing anecdotal evidence that GTN does not improve psychotic symptoms. Conclusions: We found no indication of an effect of GTN on symptoms of psychosis or cognition.

Oral nitric-oxide donor glyceryl-trinitrate induces sensitization in spinal cord pain processing in migraineurs: A double-blind, placebo-controlled, cross-over study

2011 ◽  
Vol 15 (5) ◽  
pp. 482-490 ◽  
Author(s):  
Armando Perrottal ◽  
Mariano Serraol ◽  
Cristina Tassorellil ◽  
Natalia Arce-Leall ◽  
Elena Guaschinol ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Glyceryl Trinitrate ◽  
Nitric Oxide Donor ◽  
Pain Processing ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Effect of the nitric oxide donor, glyceryl trinitrate, on human gall bladder motility

Gut ◽  
1998 ◽  
Vol 42 (3) ◽  
pp. 410-413 ◽  
Author(s):  
R Greaves ◽  
J Miller ◽  
L O’Donnell ◽  
A McLean ◽  
M J G Farthing
Keyword(s):  
Nitric Oxide ◽  
Gall Bladder ◽  
Glyceryl Trinitrate ◽  
Bladder Volume ◽  
Nitric Oxide Donor ◽  
Fasting State ◽  
Double Blind ◽  
Bladder Emptying

Background—Nitric oxide is a major neurotransmitter in non-adrenergic, non-cholinergic (NANC) pathways. NANC inhibitory innervation has been shown in human gall bladder muscle in vitro; the role of nitric oxide in human gall bladder emptying however is undefined.Aims—To study the effect of glyceryl trinitrate, a nitric oxide donor, on gall bladder emptying in healthy subjects using a randomised, double blind, crossover, placebo controlled design.Methods—Ultrasonographic gall bladder volume was measured in the fasting state in eight healthy volunteers after randomised administration of either glyceryl trinitrate 1200 μg buccal spray or placebo spray. On two further occasions, after randomised administration of either glyceryl trinitrate 1200 μg buccal spray or placebo spray, gall bladder volumes were also measured after a liquid test meal.Results—Glyceryl trinitrate significantly increased fasting gall bladder volume to a mean of 114% (SEM 5%) of pretreatment volume (p=0.039). Glyceryl trinitrate also significantly impaired gall bladder emptying between five and 40 minutes postprandially. Gall bladder ejection fraction was also reduced after glyceryl trinitrate compared with placebo (43 (6.9)% versus 68.4 (6.5)%, p=0.016).Conclusions—This study shows that glyceryl trinitrate produces gall bladder dilatation in the fasting state and reduces postprandial gall bladder emptying, suggesting that nitric oxide mechanisms may be operative in the human gall bladder in vivo.

scholarly journals Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Philip M. Bath ◽  
Lisa Woodhouse ◽  
Kailash Krishnan ◽  
Craig Anderson ◽  
Eivind Berge ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Acute Stroke ◽  
Meta Analysis ◽  
Haemorrhagic Stroke ◽  
Stroke Onset ◽  
Nitric Oxide Donor ◽  
No Donor ◽  
No Donors ◽  
Subacute Stroke

Background.Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4–6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials.Methods.Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life.Results.Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34–0.78) and reduced death (OR 0.32, 95% CI 0.14–0.78).Conclusions.NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

Role of N-acetyl-N-nitroso-tryptophan as nitric oxide donor in the modulation of HIF-1-dependent signaling

2010 ◽  
Vol 391 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Utta Berchner-Pfannschmidt ◽  
Suzan Tug ◽  
Jun Hu ◽  
Buena Delos Reyes ◽  
Joachim Fandrey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Animal Studies ◽  
Hypoxia Inducible Factor ◽  
Nitric Oxide Donor ◽  
Strong Increase ◽  
No Donor ◽  
No Donors ◽  
Hypoxic Conditions

Abstract N-Acetyl-N-nitroso-tryptophan (NANT) is well known for its capacity to generate nitric oxide (NO)-releasing compounds. It is unknown, however, whether NANT can be successfully applied as a precursor of NO in a complex biological environment such as a cell culture system. NO donors can be useful to induce the transcription factor hypoxia-inducible factor 1 (HIF-1) that coordinates the protection of cells and tissues from the lack of oxygen, termed hypoxia. HIF-1 degradation is controlled by prolyl hydroxylase 2 (PHD2) which needs to be inhibited for HIF-1 accumulation. Here, the effects of NANT in inhibiting recombinant PHD2 and up-regulating of HIF-1 and HIF-1-mediated carboanhydrase-9 (CA9) mRNA expression were compared in living cells with the NO donors N-nitrosomelatonin (NOMela) and S-nitrosoglutathione (GSNO) under normoxic and hypoxic conditions. In contrast to GSNO, NANT was similar to NOMela being highly effective in inhibiting recombinant PHD2. NANT-mediated activation of HIF-1 in oxygenated cells was comparable to hypoxic activation of HIF-1 in all cases. In contrast, under hypoxia NANT was able to boost hypoxic cellular HIF-1 levels by further reducing the activity of cellular PHD2. The strong increase of HIF-dependent CA9 mRNA expression demonstrated that NANT-induced HIF-1 was transcriptionally active. Finally, the efficacy of NANT to increase both HIF-1 and CA9 mRNA did not depend on the absolute conformation of the tryptophan moiety. In conclusion, NANT appears to be an excellent NO donor for cells in culture and l-NANT should be useful for in vivo animal studies.

Transdermal Nitroglycerine in the Management of Pain Associated with Primary Dysmenorrhoea: A Multinational Pilot Study

1997 ◽  
Vol 25 (1) ◽  
pp. 41-44 ◽  
Author(s):  
O Ré ◽  
Keyword(s):  
Nitric Oxide ◽  
Pain Relief ◽  
Muscle Relaxation ◽  
Nitric Oxide Donor ◽  
Controlled Study ◽  
Smooth Muscle Relaxation ◽  
Uterine Contractility ◽  
Double Blind ◽  
Patch Application ◽  
Endogenous Nitric Oxide

Endogenous nitric oxide mediates smooth-muscle relaxation with subsequent vasodilatation in the vascular, pulmonary, gastrointestinal and genitourinary tissues. Transdermal nitroglycerine (a nitric oxide donor) has been found effective in inhibiting uterine contractility during premature labour. Sixty-five women with histories of moderate-to-severe pain associated with menses were treated with nitroglycerine patches that delivered 0.2 or 0.1 mg/h. Patches were applied as necessary during the first 3 days of the menstrual cycle for up to three consecutive cycles. Pain intensity was assessed at baseline and at 30 min and at 1, 2 and 4 h after patch application. Most patients obtained pain relief with the first dose of the first day. Pain relief was satisfactory to excellent in 90% of the patients. Headache was reported by 20% of the patients, most often in patients using two consecutive patches. A randomized, double-blind, placebo-controlled study is underway in an attempt to confirm the above findings.

Skeletal muscle force and actomyosin ATPase activity reduced by nitric oxide donor

1997 ◽  
Vol 83 (4) ◽  
pp. 1326-1332 ◽  
Author(s):  
William J. Perkins ◽  
Young-Soo Han ◽  
Gary C. Sieck
Keyword(s):  
Nitric Oxide ◽  
Mechanical Properties ◽  
Atpase Activity ◽  
Muscle Force ◽  
Isometric Force ◽  
Nitric Oxide Donor ◽  
No Donor ◽  
Single Fibers ◽  
Actomyosin Atpase ◽  
Cross Bridge

Perkins, William J., Young-Soo Han, and Gary C. Sieck.Skeletal muscle force and actomyosin ATPase activity reduced by nitric oxide donor. J. Appl. Physiol.83(4): 1326–1332, 1997.—Nitric oxide (NO) may exert direct effects on actin-myosin cross-bridge cycling by modulating critical thiols on the myosin head. In the present study, the effects of the NO donor sodium nitroprusside (SNP; 100 μM to 10 mM) on mechanical properties and actomyosin adenosinetriphosphatase (ATPase) activity of single permeabilized muscle fibers from the rabbit psoas muscle were determined. The effects of N-ethylmaleimide (NEM; 5–250 μM), a thiol-specific alkylating reagent, on mechanical properties of single fibers were also evaluated. Both NEM (≥25 μM) and SNP (≥1 mM) significantly inhibited isometric force and actomyosin ATPase activity. The unloaded shortening velocity of SNP-treated single fibers was decreased, but to a lesser extent, suggesting that SNP effects on isometric force and actomyosin ATPase were largely due to decreased cross-bridge recruitment. The calcium sensitivity of SNP-treated single fibers was also decreased. The effects of SNP, but not NEM, on force and actomyosin ATPase activity were reversed by treatment with 10 mMdl-dithiothreitol, a thiol-reducing agent. We conclude that the NO donor SNP inhibits contractile function caused by reversible oxidation of contractile protein thiols.

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