Interaction of glyceryl trinitrate and sodium nitroprusside with bovine pulmonary vein homogenate and 10,000 x g supernatant: biotransformation and nitric oxide formation.
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 x 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 x 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.
Marks
G S
GS
Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, Ont., Canada.
McLaughlin
B E
BE
Brown
L B
LB
Beaton
D E
DE
Booth
B P
BP
Nakatsu
K
K
Brien
J F
JF
D000818:Animals; D001711:Biotransformation; D002417:Cattle; D002849:Chromatography, Gas; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D011667:Pulmonary Veins / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D009599:Nitroprusside; D009569:Nitric Oxide; D005996:Nitroglycerin