WHOLE-BODY ARGININE METABOLISM AND NITRIC-OXIDE SYNTHESIS IN NEWBORNSWITH PERSISTENT PULMONARY-HYPERTENSION

Despite the potential relevance of the L-arginine-nitric oxide (NO) pa thway in the pathophysiology of pulmonary hypertension, no in vivo stu dies of the kinetics of arginine and NO have been conducted previously in this population. The terminal guanidino N-atom of L-arginine is th e precursor for NO, which is oxidized to the stable inorganic nitrogen oxides, nitrite (NO2-) and nitrate (NO3-). Thus, synthesized NO is de tected in serum or urine as NO2- and NO3-. The purpose of this investi gation was to compare studies of whole body arginine metabolism twice in nine patients with persistent pulmonary hypertension of the newborn (PPHN), using a primed constant i.v. infusion of L- [guanidino-N-15(2 ),5,5(2)H(2)] arginine and L-[5,5,5(2)H(3)]leucine, first during acute pulmonary vasoconstriction and again during convalescence, and thereb y to characterize quantitative aspects of whole body arginine kinetics and NO production, as estimated from the rate of transfer of the N-15 -guanidino-label of arginine to urinary nitrate ((NO3-)-N-15). Arginin e flux rates were 84.1 +/- 8.6 mu mol . kg .(-1)h(-1) (mean +/- SEM) d uring acute pulmonary hypertension and increased to 125 +/- 13.2 (p < 0.05) during convalescence, whereas leucine fluxes were unchanged (168 .5 +/- 15 versus 178.8 +/- 10.2 mu mol . kg .(-1)h(-1)), and comparabl e to those reported in healthy newborns. During convalescence total ur inary nitrate excreted increased by 66% (p < 0.05), urinary (NO3-)-N-1 5, increased from 0.29 +/- 0.07 to 0.74 +/- 0.15 mu mol . d(-1) (p < 0 .05), and the rate of plasma arginine conversion to NO increased from 10.3 +/- 2.2 to 45.6 +/- 13 mu mol . d(-1) (p < 0.05). This study indi cates a decreased plasma arginine utilization for whole body NO synthe sis during the acute vasoconstrictive state of PPHN and suggests that arginine availability may become an important factor in NO formation.