Nitrate biosynthesis in rats, ferrets and humans. Precursor studies with L-arginine.
L-Arginine, the primary nitrogen source for nitric oxide synthesized by many cell types in culture and for biosynthesized nitrate in humans, is also a nitrogen source for biosynthesized nitrate in rats and ferrets. After administration of [15N2]L-arginine to rats and ferrets, [15N]NO3- was detected in urine. Escherichia coli lipopolysaccharide induced more than a 10-fold increase in urinary nitrate in rats and a parallel increase in incorporation of 15N from [15N2]L-arginine into NO3-. Bradykinin, a vasodilator which induces nitric oxide production by endothelial cells in vitro, lacked detectable effect on urinary nitrate or on incorporation of L-arginine nitrogen into nitrate in rats. A prolonged period of vasodilation brought on by an extended period of exercise increased urinary nitrate 2-fold in human subjects. In the rat, recoveries in 24 h post-dose urine collections of [15N]NO3- given i.v. and i.p. were 75 and 64% respectively, while in the ferret, recoveries of i.v. and per os [15N]NO3- doses were 49 and 34% respectively. Thus, nitrate synthesized by mammalian cells in vivo would undergo losses similar to those for exogenous nitrate.
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C D
CD
Division of Toxicology, Whitaker College, Cambridge, MA.
Wishnok
J S
JS
Hurley
J P
JP
Rosenblad
W D
WD
Fox
J G
JG
Tannenbaum
S R
SR
D000328:Adult; D000818:Animals; D001120:Arginine / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D005289:Ferrets; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D009566:Nitrates / Q000008:administration & dosage / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D009590:Nitrogen Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains
D009566:Nitrates; D009590:Nitrogen Radioisotopes; D001120:Arginine; D009584:Nitrogen