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.

scholarly journals Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle

2002 ◽  
Vol 282 (5) ◽  
pp. H1787-H1792 ◽  
Author(s):  
Moshe Swissa ◽  
Toshihiko Ohara ◽  
Moon-Hyoung Lee ◽  
Sanjay Kaul ◽  
Prediman K. Shah ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Donor ◽  
Tyrode Solution ◽  
No Donor ◽  
Maximum Slope ◽  
No Donors ◽  
Restitution Curve ◽  
Rapid Pacing ◽  
Drug Free ◽  
Endocardial Activation

We tested the hypothesis that sildenafil, singly or in combination with nitric oxide (NO) donors, promotes ventricular tachycardia (VT) and ventricular fibrillation (VF). Vulnerability to VT/VF was tested by rapid pacing in eight isolated normal swine right ventricles (RV). The endocardial activation was optically mapped, and the dynamic action potential duration (APD) restitution curves were constructed with metal microelectrodes. At baseline, no VT/VF could be induced. Sildenafil (0.2 μg/ml) or NO donor singly or in combination did not alter VT/VF vulnerability. However, when 2 μg/ml sildenafil was combined with NO donors, the incidence of VT and VF rose significantly ( P < 0.01). VT with a single periodic wavefront was induced in five of eight RVs, and VF with multiple wavefronts was induced in all eight RVs. The sildenafil-NO donor pro-VT/VF combination significantly increased the maximum slope of the APD restitution curve and the amplitude of the APD alternans. The pro-VT/VF effects of sildenafil were reversible after drug-free Tyrode solution perfusion. We conclude that a sildenafil (2 μg/ml) and NO donor combination increases VT/VF vulnerability in the normal RV by a mechanism compatible with the restitution hypothesis.

Effect of in vivo nitrate tolerance on hypersensitivity to NO donors after NO-synthase blockade

2002 ◽  
Vol 80 (11) ◽  
pp. 1106-1118 ◽  
Author(s):  
Jodan D Ratz ◽  
Michael A Adams ◽  
Brian M Bennett
Keyword(s):  
Nitric Oxide ◽  
Glyceryl Trinitrate ◽  
Nitrate Tolerance ◽  
Metabolite Formation ◽  
No Donor ◽  
No Donors ◽  
Nos Inhibitors ◽  
Pressure Lowering ◽  
Oxide Synthase

Animals treated with nitric oxide synthase (NOS) inhibitors exhibit marked hypersensitivity to the blood pressure lowering effects of exogenous nitric oxide (NO) donors. We used this model as a sensitive index to evaluate the relative importance of reduced biotransformation of glyceryl trinitrate (GTN) to NO in the development of nitrate tolerance. NOS-blockade hypertension using NG-nitro-L-arginine methyl ester (L-NAME) caused a marked enhancement of the mean arterial pressure (MAP) decrease mediated by GTN in nontolerant rats. However, even large doses of GTN were unable to change the MAP in GTN-tolerant, NOS-blockade hypertensive animals. In contrast, the MAP responses to the spontaneous NO donor sodium nitroprusside (SNP) were completely unaltered in either tolerant rats or tolerant NOS-blockade hypertensive animals, indicating that NO-dependent vasodilatory mechanisms remain intact despite the development of GTN tolerance. The MAP-lowering effects of GTN in NOS-blockade hypertensive animals were restored 48 h after cessation of chronic GTN exposure. These alterations in the pharmacodynamic response to GTN during tolerance development and reversal were associated with parallel changes in the pattern of GTN metabolite formation, suggesting that the activity of one or more enzymes involved in nitrate metabolism was altered as a consequence of chronic GTN exposure. These findings suggest that the vasodilation resulting from the vascular biotransformation of GTN to NO (or a closely related species) is severely compromised in nitrate-tolerant animals, and that although other mechanisms may contribute to the vascular changes observed following the development of GTN tolerance, decreased GTN bioactivation is likely the most important.Key words: biotransformation, glyceryl trinitrate, hypertension, nitric oxide, tolerance.

scholarly journals Involvement of nitric oxide donor compounds in the bactericidal activity of human neutrophils in vitro

2003 ◽  
Vol 52 (4) ◽  
pp. 303-308 ◽  
Author(s):  
Magdalena Klink ◽  
Maciej Cedzyński ◽  
Anna St Świerzko ◽  
Henryk Tchórzewski ◽  
Zofia Sulowska
Keyword(s):  
Nitric Oxide ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Bactericidal Activity ◽  
Nitric Oxide Donor ◽  
Human Neutrophils ◽  
Bacterial Strains ◽  
No Donor ◽  
No Donors

The bactericidal activity of human neutrophils against extracellular and facultatively intracellular bacteria was studied in the presence of the nitric oxide (NO) donors sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), a molsidomine metabolite. SNP and molsidomine are drugs commonly used as nitrovasodilators in coronary heart disease. It is demonstrated here that the NO donor compounds themselves did not affect the viability and survival of the bacterial strains tested. Neither SNP nor SIN-1 had any effect on the process of bacteria ingestion. In contrast, NO donors enhanced the ability of neutrophils to kill Escherichia coli, Proteus vulgaris and Salmonella Anatum. However, strains differed in their susceptibility to SNP- and SIN-1-mediated killing by neutrophils. Removal of the superoxide anion reduced the bactericidal activity of SNP- and SIN-1-treated neutrophils against E. coli and S. Anatum. This suggests that the NO derivatives formed in the reaction of NO generated from donors with the reactive oxygen species released by phagocytosed neutrophils potentiate the bactericidal activity of human neutrophils in vitro. The above original observation discussed here suggests clinical significance for the treatment of patients with nitrovasodilators in the course of coronary heart disease therapy.

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.

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.

The Effect of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Blood Pressure and Platelet Function in Acute Stroke

2001 ◽  
Vol 11 (3) ◽  
pp. 265-272 ◽  
Author(s):  
Philip M.W. Bath ◽  
Rohan Pathansali ◽  
Robert Iddenden ◽  
Fiona J. Bath
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Glyceryl Trinitrate ◽  
Acute Stroke ◽  
Platelet Function ◽  
Nitric Oxide Donor

A review of the synthesis of nitric oxide donor and donor derivatives with pharmacological activities

2021 ◽  
Vol 21 ◽  
Author(s):  
Kexin Wang ◽  
Yue Wang ◽  
Hualin Zhang ◽  
Xintong Li ◽  
Weina Han
Keyword(s):  
Nitric Oxide ◽  
The Body ◽  
Nitric Oxide Donor ◽  
Pharmacological Activities ◽  
No Donor ◽  
No Donors ◽  
Physiological Conditions ◽  
Gaseous Substance ◽  
Human Need ◽  
Endogenous Nitric Oxide

: Abstract Endogenous nitric oxide (NO) is an important effector molecule and signal transduction molecule, which participates in the regulation of multiple functions in organisms, involving a variety of physiological and pathological processes, especially playing a very important role in the cardiovascular, immune, and nervous systems. NO is a gaseous substance with a short half-life in the body and is unstable in aqueous solutions. Therefore, many researchers focus on the release and activity of NO donors and their derivatives. However, NO donors can release free NO or NO analogues under physiological conditions to meet the human need. NO donors can be coupled with the corresponding active basic nucleus, so that they have the biological activity derived from both the basic nucleus and the NO donors, thus performing better bioactivity. This paper reviewed the routes of synthesis and advance activities of NO donor derivatives.

Sign in / Sign up

Export Citation Format

Share Document