نتایج جستجو برای: مدل gtn

تعداد نتایج: 120569  

2005
PAUL W. ARMSTRONG

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...

Journal: :The Journal of pharmacology and experimental therapeutics 2000
J D Ratz A B Fraser K J Rees-Milton M A Adams B M Bennett

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...

Journal: :Molecular pharmacology 2003
Jon DiFabio Yanbin Ji Vasilis Vasiliou Gregory R J Thatcher Brian M Bennett

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...

Journal: :The Journal of pharmacology and experimental therapeutics 1997
R Yuan M Sumi L Z Benet

Nitroglycerin (GTN) has been used to treat heart disease for many years. It is generally believed that GTN is a prodrug; however, the mechanism for GTN bioactivation remains unknown. Recent studies, using hepatic microsomes, have suggested the involvement of cytochrome P450 3A (CYP3A) in GTN biotransformation. Here, we used an animal model to test the hypothesis that aortic CYP3A plays a role i...

Journal: :Circulation 1980
P W Armstrong J A Armstrong G S Marks

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...

Journal: :The Journal of pharmacology and experimental therapeutics 2006
Yanbin Ji Brian M Bennett

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 ...

Journal: :The Journal of pharmacology and experimental therapeutics 2006
Jonathan M DiFabio George R Thomas Liana Zucco Michael A Kuliszewski Brian M Bennett Michael J Kutryk John D Parker

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...

Journal: :The Journal of pharmacology and experimental therapeutics 1997
J D Parker A B Parker B Farrell J O Parker

It has been reported that nitroglycerin (GTN) tolerance can be prevented by the concurrent administration of hydralazine. Although the mechanism of this effect remains unknown, it is possible that hydralazine modifies counter-regulatory responses to nitrate administration. To address this question, we examined the impact of hydralazine therapy on the development of tolerance during sustained th...

2016
Marissa Opelt Emrah Eroglu Markus Waldeck-Weiermair Michael Russwurm Doris Koesling Roland Malli Wolfgang F. Graier John T. Fassett Astrid Schrammel Bernd Mayer

Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN), resulting in activation of soluble guanylate cyclase (sGC) and cGMP-mediated vasodilation. We have previously shown that a minor reaction of ALDH2-catalyzed GTN bioconversion, accounting for about 5% of the main clearance-based turnover yielding inorganic nitrite, results in direct NO ...

Journal: :Journal of the American College of Cardiology 2011
Andrew Liuni Mary Clare Luca Giuseppe Di Stolfo Amar Uxa Justin A Mariani Tommaso Gori John D Parker

OBJECTIVES We aimed to assess whether concurrent administration of atorvastatin would modify the development of tolerance and endothelial dysfunction associated with sustained nitroglycerin (GTN) therapy in humans. BACKGROUND Animal studies have demonstrated that administration of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors can protect against GTN-induced endothelial dysfunctio...

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