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© 1990 Oxford University Press

other

Nitrat biosynthesis in rats, ferrets and humans. Precursor studies with L-arginine

Cynthia D. Leaf 1, John S. Wishnok 1, John P. Hurley 3, William D. Rosenblad 3, James G. Fox 1 3 and Steven R. Tannenbaum 1 2 4

1Division of Toxicology, Whitaker College Cambridge, MA 02139, USA
2Department of Chemistry Cambridge, MA 02139, USA
3Division of Comparative Mcdicine, Massachusetts Institute of Technology. Cambridge, MA 02139, USA

4To whom correspondence should be addressed

L-Arglnine, the primary nitrogen source for nitric oxide synthesized by many cell types in culture and for bio-synthesized 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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