KINETICS OF NITROGEN-OXIDE PRODUCTION FOLLOWING EXPERIMENTAL THERMAL-INJURY IN RATS

Nitric oxide is biosynthesized from the amino acid L-arginine by the e nzyme nitric oxide synthase. Nitric oxide is a vasodilator, a neurotra nsmitter, and may modulate immune function. The experiments presented here were performed to determine whether the synthesis of nitric oxide is increased following experimental burn injury in rats. After a 30% total body surface area burn in 300-g Lewis rats, the urinary output o f nitrate, a stable metabolite of nitric oxide, was significantly incr eased for 8 days postburn compared with that in sham-burned control ra ts. The origin of the urinary nitrate from L-arginine was demonstrated by administering the stable isotope N-15(2)-guanido-arginine to burne d and sham-burned rats and observing an immediate enrichment of N-15 i n nitrate. The amount of administered N-15 recovered as (NO3)-N-15 was < 1% of the administered arginine isotope in both the burned and unbu rned rats; the recovery of the isotope increased tenfold over baseline recovery in burned rats. The arginine analog N-monomethyl-arginine, a n inhibitor of the enzyme nitric oxide synthase, blocked the postburn rise in urinary NO3 output in burned rats, but did not completely inhi bit the output of NO3 in burn wound-infected rats. Experimental burn i njury in rats results in an increase in L-arginine-dependent nitric ox ide production and urinary nitrate output.