Selective Arterial Dilatation by Glyceryl Trinitrate Is Not Associated with Nitric Oxide Formation in vitro

2008 ◽  
Vol 45 (5) ◽  
pp. 375-385 ◽  
Author(s):  
Mark R. Miller ◽  
Stuart Grant ◽  
Roger M. Wadsworth
1994 ◽  
Vol 113 (4) ◽  
pp. 1508-1514 ◽  
Author(s):  
Aman S. Hussain ◽  
Margo Poklewska-Koziell ◽  
James F. Brien ◽  
Gerald S. Marks ◽  
Kanji Nakatsu

1992 ◽  
Vol 70 (6) ◽  
pp. 935-937 ◽  
Author(s):  
Gerald S. Marks ◽  
Brian E. McLaughlin ◽  
Kanji Nakatsu ◽  
James F. Brien

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.


2010 ◽  
Vol 49 ◽  
pp. S14
Author(s):  
Jefferson Henrich Amaral ◽  
Marcelo Montenegro ◽  
Lucas Pinheiro ◽  
Graziele Ferreira ◽  
Jose Eduardo Tanus Santos

1992 ◽  
Vol 70 (2) ◽  
pp. 308-311 ◽  
Author(s):  
Gerald S. Marks ◽  
Brian E. McLaughlin ◽  
Kanji Nakatsu ◽  
James F. Brien

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.


Nitric Oxide ◽  
2011 ◽  
Vol 24 ◽  
pp. S31
Author(s):  
Jefferson Amaral ◽  
Marcelo Montenegro ◽  
Lucas Pinheiro ◽  
Graziele Ferreira ◽  
José Eduardo Tanus-Santos

1991 ◽  
Vol 69 (6) ◽  
pp. 889-892 ◽  
Author(s):  
Gerald S. Marks ◽  
Brian E. McLaughlin ◽  
Leslie B. Brown ◽  
Danielle E. Beaton ◽  
Brian P. Booth ◽  
...  

The current proposed mechanism of action of nitrovasodilator drugs involves biotransformation to nitric oxide, which is postulated to be the active vasodilator substance. Our objective was to determine whether nitric oxide was formed from two prototype nitrovasodilator drugs, glyceryl trinitrate (GTN) and sodium nitroprusside (SNP), after incubation with bovine pulmonary vein (BPV) preparations. GTN or SNP was incubated in an argon atmosphere with phosphate buffer, BPV homogenate, or the 10 000 × g supernatant fraction of the homogenate. Nitric oxide formation, as determined by a chemiluminescence – headspace gas method, was measurable following the incubation of SNP with BPV homogenate and 10 000 × g supernatant. There was no detectable formation of nitric oxide from the incubation of GTN with the two BPV preparations, although GTN was biotransformed to glyceryl dinitrate, as determined by gas–liquid chromatography. There was decreased recovery of nitric oxide during the incubation of authentic nitric oxide with the two BPV preparations as compared with buffer. In conclusion, formation of nitric oxide was measured for the interaction of SNP, but not GTN, with BPV preparations. However, the data do not exclude the possible formation of nitric oxide from GTN, as nitric oxide was shown to be sequestered or transformed by the BPV preparations.Key words: glyceryl trinitrate, sodium nitroprusside, nitric oxide formation, bovine pulmonary vein.


Diabetes ◽  
1992 ◽  
Vol 41 (4) ◽  
pp. 552-556 ◽  
Author(s):  
J. A. Corbett ◽  
R. G. Tilton ◽  
K. Chang ◽  
K. S. Hasan ◽  
Y. Ido ◽  
...  

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