Gastric nitrate reduction and nitrosation of trimethylurea in swine treated with pentagastrin or cimetidine.
Swine were treated with cimetidine in order to quantify the reduction of nitrate to nitrite and the gastric formation of N-nitrosotrimethylurea (NTMU) under conditions similar to those in the achlorhydric human stomach. Gastric-fistulated swine were instilled with 6.0 mmol of nitrate in 50 ml water, after which gastric nitrate, nitrite and pH were monitored. Trimethylurea, 250 mumol in 50 ml water, was instilled via the fistula 10 min following the peak gastric nitrite concentration. Similar experiments were conducted with pentagastrin-stimulated animals, in order to quantitate the effect of gastric pH and microflora on the presence of nitrate, nitrite and NTMU formation. The stomachs of cimetidine-treated pigs (elevated pH) were colonized by nitrate reductase organisms to levels of 10(4)-10(7)/ml gastric fluid. Gastric nitrite concentration in cimetidine-treated animals reached a maximum of 370-2085 microM, 60 min following the nitrate dose. Trimethylurea was only marginally nitrosated (less than 0.1 mumol/l gastric fluid) in cimetidine- or pentagastrin-stimulated animals. The low yield of NTMU at elevated pH, in the presence of substantial nitrite, suggests that the nitrate-reducing bacteria present in the porcine stomach did not catalyze trimethylurea nitrosation in vivo.
Maragos
C M
CM
Institute for Comparative and Environmental Toxicology, Cornell University, Ithaca, NY 14853.
Klausner
K A
KA
Shapiro
K B
KB
Hotchkiss
J H
JH
D000818:Animals; D001419:Bacteria / Q000378:metabolism; D002927:Cimetidine / Q000494:pharmacology*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000378:metabolism*; D008782:Methylurea Compounds / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction; D010418:Pentagastrin / Q000494:pharmacology*; D013552:Swine
D008782:Methylurea Compounds; D009566:Nitrates; D009603:Nitroso Compounds; D002927:Cimetidine; D010418:Pentagastrin