Direct demonstration of nitric oxide formation in organs of rabbits treated by transdermal glyceryl trinitrate using an in vivo spin trapping technique

Incubation of glyceryl trinitrate (GTN) with 5% (w/v) rat brain homogenate (RBH) resulted in biotransformation of the organic nitrate vasodilator drug to a mixture of glyceryl-1,2-dinitrate (1,2-GDN) and glyceryl-1,3-dinitrate (1,3-GDN). Heating of the RBH at 100 °C for 5 min and (or) pretreatment with 5 mM N-ethylmaleimide at 37 °C for 10 min demonstrated that about two-thirds of the GTN biotransformation activity was due to a sulfhydryl-dependent enzymatic process resulting in the predominant formation of 1,2-GDN, and that the remaining biotransformation activity was due to a sulfhydryl-dependent nonenzymatic process resulting in the selective formation of 1,3-GDN. In a preliminary experiment, nitric oxide formation was observed during the incubation of GTN with RBH under anaerobic conditions. These data support the idea that some of the therapeutic and adverse effects of GTN are mediated through its action in the central nervous system.Key words: glyceryl trinitrate, biotransformation, rat brain homogenate, sulfhydryl-dependent enzyme, nitric oxide formation.

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Continuous monitoring of in vivo hepatic nitric oxide formation using EPR trapping analysis in biliary flow

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(98)90323-9 ◽

1998 ◽

Vol 25 ◽

pp. S105

Author(s):

Yashige Kotake ◽

Danny R. Moore ◽

Hong Sang ◽

Lester A. Reinke

Keyword(s):

Nitric Oxide ◽

Continuous Monitoring ◽

Oxide Formation ◽

Nitric Oxide Formation

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In vivo monitoring of radiation-induced hepatic nitric oxide formation. Inhibition by antioxidants

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(98)90334-3 ◽

1998 ◽

Vol 25 ◽

pp. S108

Author(s):

Hong Sang ◽

Yashige Kotake ◽

Danny R. Moore ◽

Lester A. Reinke ◽

Toshihiko Ozawa

Keyword(s):

Nitric Oxide ◽

Oxide Formation ◽

In Vivo Monitoring ◽

Nitric Oxide Formation ◽

Radiation Induced

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Characterization of nitric oxide formation by stimulated endothelial, neuroblastoma and macrophage cells using spin trapping techniques

Pharmacological Research ◽

10.1016/s1043-6618(09)80077-7 ◽

1990 ◽

Vol 22 ◽

pp. 21

Author(s):

Carmen M. Arroyo

Keyword(s):

Nitric Oxide ◽

Spin Trapping ◽

Oxide Formation ◽

Macrophage Cells ◽

Nitric Oxide Formation

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Tempol Enhances the Nitrite-derived Nitric oxide Formation in Vitro and in Vivo

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2010.10.003 ◽

2010 ◽

Vol 49 ◽

pp. S14

Author(s):

Jefferson Henrich Amaral ◽

Marcelo Montenegro ◽

Lucas Pinheiro ◽

Graziele Ferreira ◽

Jose Eduardo Tanus Santos

Keyword(s):

Nitric Oxide ◽

Oxide Formation ◽

Nitric Oxide Formation

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Direct evidence for nitric oxide formation from glyceryl trinitrate during incubation with intact bovine pulmonary artery

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-039 ◽

1992 ◽

Vol 70 (2) ◽

pp. 308-311 ◽

Cited By ~ 33

Author(s):

Gerald S. Marks ◽

Brian E. McLaughlin ◽

Kanji Nakatsu ◽

James F. Brien

Keyword(s):

Nitric Oxide ◽

Pulmonary Artery ◽

Glyceryl Trinitrate ◽

Direct Evidence ◽

Oxide Formation ◽

Chemiluminescence Method ◽

Nitric Oxide Formation ◽

Headspace Gas ◽

Vasodilator Action ◽

Chemiluminescence Detector

It has been proposed that the mechanism of the vasodilator action of glyceryl trinitrate (GTN) involves biotransformation to nitric oxide. A sensitive chemiluminescence method for nitric oxide determination was used to test this hypothesis. In four experiments, bovine pulmonary artery (BPA) was incubated with GTN (0.1 mM) in Krebs' solution (2 mL) containing 30 mM KCl, and in anaerobic conditions using 95% Ar – 5% CO2, in a sealed micro-Fernbach flask (6.2-mL volume). After incubation for 2, 5, 10, or 20 min at 37 °C, 400-μL aliquots of headspace gas were removed and injected into a redox chemiluminescence detector. Nitric oxide formation was first measurable at 5 min (76 ± 53 pmol/g wet wt. BPA), and increased with incubation time (174 ± 46 pmol/g wet wt. BPA after 10 min and 310 ± 67 pmol/g wet wt. BPA after 20 min). This is the first direct chemical measurement of nitric oxide formation during interaction of GTN with vascular smooth muscle. These data support the concept that GTN is a nitrovasodilator prodrug acting via the formation of nitric oxide.Key words: nitric oxide formation, glyceryl trinitrate, chemiluminescence, bovine pulmonary artery, vasodilation.

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