BACKGROUND AND PURPOSE The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed. METHODS We performed a randomized controlled trial with screening, consent, randomization, and treatment performed by paramedics prior to hospitalization. Patients with probable ultra-acute stroke ...

OBJECTIVES We tested the hypothesis of whether an inhibition of the nitroglycerin (GTN) bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) contributes to GTN tolerance in human blood vessels. BACKGROUND The hemodynamic effects of GTN are rapidly blunted by the development of tolerance, a phenomenon associated with increased formation of reactive oxygen species (ROS). Recent st...

The role of nitric oxide (NO) and thiol-containing compounds in glyceryl trinitrate (GTN)-induced vasodilation was investigated using the thiol-alkylating agent N-ethylmaleimide (NEM). Bovine pulmonary artery (BPA) rings were submaximally contracted with K+ and exposed to increasing concentrations of GTN after a 30-min incubation with 50 microM NEM. NEM decreased maximal relaxation (10 microM G...

OBJECTIVE To address the role of epigenetic enzymes in the process of arterial vasorelaxation and nitrate tolerance, in vitro and in vivo experiments were performed in the presence or absence of glyceryl trinitrate (GTN) or histone deacetylases/histone acetylases modulators. METHODS AND RESULTS In vitro single GTN administration rapidly increased cGMP synthesis and protein N(ε)-lysine acetyla...

The effects of nitroglycerin (glyceryl trinitrate - GTN) are mediated by liberated nitric oxide (NO) and formed reactive nitrogen species, which induces oxidative stress during biotransformation in red blood cells (RBCs). The aim of this study was to evaluate effects of GTN on antioxidative defense system (AOS) in rat erythrocytes (without) and reticulocytes (with functional mitochondria). Rat ...

Background—Sublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to vasodilate maximally the epicardial coronary arteries during coronary angiography. Objective—To compare the coronary vasodilatory eVects of GTN capsules and ISDN spray with those induced by intracoronary GTN using quantitative coronary an...

GTN (nitroglycerin; glycerol trinitrate) causes dilation of blood vessels via activation of nitric oxide (NO)-sensitive sGC (soluble guanylate cyclase), a heterodimeric haem protein that catalyses the conversion of GTP into cGMP. Activation of sGC by GTN requires enzymatic or non-enzymatic bioactivation of the nitrate. Based on insufficient NO release and lack of spectroscopic evidence for form...

BACKGROUND Sublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to vasodilate maximally the epicardial coronary arteries during coronary angiography. OBJECTIVE To compare the coronary vasodilatory effects of GTN capsules and ISDN spray with those induced by intracoronary GTN using quantitative coronary...

OBJECTIVE Nitrate tolerance is likely attributable to an increased production of reactive oxygen species (ROS) leading to an inhibition of the mitochondrial aldehyde dehydrogenase (ALDH-2), representing the nitroglycerin (GTN) and pentaerythrityl tetranitrate (PETN) bioactivating enzyme, and to impaired nitric oxide bioactivity and signaling. We tested whether differences in their capacity to i...

Sustained nitroglycerin (GTN) therapy impairs endothelial function in healthy volunteers and patients with cardiovascular disease, caused by an increase in vascular oxidative stress. This study aims to estimate the effect of rosiglitazone on vascular endothelial function in healthy volunteers continuously dosed to transdermal GTN (0.6mg/hr) for 7 days. To assess endothelial function, forearm bl...