The expanding role of intravenous nitroglycerin (GTN) in the management of critically ill hospitalized patients demands a clear knowledge of its pharmacodynamics and kinetics in both normal and diseased states. Accordingly, we studied 16 patients with congestive cardiac failure to establish the relationship between blood levels of GTN and its physiologic effects during and after an i.v. infusio...

There is evidence that increased endothelial production of endothelin-1 (ET-1) may contribute to glyceryl trinitrate (GTN) tolerance. We used the competitive ET(A) receptor antagonist ZD2574 to determine whether chronic ET(A) receptor blockade affected the biochemical and functional responses to GTN during the development of GTN tolerance in vivo. Tolerance induced using transdermal GTN patches...

Glyceryl trinitrate (GTN) is used in the treatment of angina pectoris and cardiac failure, but the rapid onset of GTN tolerance limits its clinical utility. Research suggests that a principal cause of tolerance is inhibition of an enzyme responsible for the production of physiologically active concentrations of NO from GTN. This enzyme has not conclusively been identified. However, the mitochon...

The expanding role of intravenous nitroglycerin (GTN) in the management of critically ill hospitalized patients demands a clear knowledge of its pharmacodynamics and kinetics in both normal and diseased states. Accordingly, we studied 16 patients with congestive cardiac failure to establish the relationship between blood levels of GTN and its physiologic effects during and after an i.v. infusio...

Although the biotransformation of organic nitrates by the cytosolic glutathione S-transferases (GSTs) is well known, the relative contribution of the microsomal GST (MGST1) to nitrate biotransformation has not been described. We therefore compared the denitration of glyceryl trinitrate (GTN) by purified rat liver MGST1 and cytosolic GSTs. Both MGST1 and cytosolic GSTs catalyzed the denitration ...

Endothelial progenitor cells (EPCs) participate in angiogenesis and the response to chronic ischemia. Risk factors and cardiovascular disease attenuate EPC number, function, and survival. Continuous therapy with nitroglycerin (glyceryl trinitrate; GTN) is associated with increased vascular oxidative stress, leading to nitrate tolerance and endothelial dysfunction. Thus, GTN therapy may also aff...

The aim of the present study was to investigate the effect of the nitric oxide signaling pathway on immune escape; thus, a tumorigenesis model was established using nude mice. The mice were inoculated with pancreatic carcinoma cells and divided into two groups, a glyceryl trinitrate (GTN) and a placebo group. When tumor volumes reached 150 mm3, the mice in the GTN group were treated with GTN tr...

Glycerol trinitrate reductase (NerA) from Agrobacterium radiobacter, a member of the old yellow enzyme (OYE) family of oxidoreductases, was expressed in and purified from Escherichia coli. Denaturation of pure enzyme liberated flavin mononucleotide (FMN), and spectra of NerA during reduction and reoxidation confirmed its catalytic involvement. Binding of FMN to apoenzyme to form the holoenzyme ...

BACKGROUND It has recently been shown that mitochondrial aldehyde dehydrogenase 2 (mtALDH) catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from nitroglycerin (glyceryl trinitrate [GTN]) within mitochondria, leading to production of cGMP and vasorelaxation. However, whether this mechanism operates in the systemic and coronary beds that subserve the antianginal action of GTN is not ...