Whole body arginine metabolism and nitric oxide synthesis in newborns with persistent pulmonary hypertension

L. Castillo, T. De Rojas-Walker, Y. M. Yu, M. Sanchez, T. E. Chapman, D. Shannon, S. Tannenbaum, J. F. Burke, V. R. Young

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Despite the potential relevance of the L-arginine-nitric oxide (NO) pathway in the pathophysiology of pulmonary hypertension, no in vivo studies of the kinetics of arginine and NO have been conducted previously in this population. The terminal gua-nidino N-atom of L-arginine is the precursor for NO, which is oxidized to the stable inorganic nitrogen oxides, nitrite (NO2) and nitrate (NO3). Thus, synthesized NO is detected in serum or urine as NO2 and NO3. The purpose of this investigation 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-[guanidine-15N2,5,52H2]arginine and L-[5,5,52H3]leucine, first during acute pulmonary vasoconstriction and again during convalescence, and thereby to characterize quantitative aspects of whole body arginine kinetics and NO production, as estimated from the rate of transfer of the15N-guanidino-label of arginine to urinary nitrate (15NO3). Arginine flux rates were 84.1 ± 8.6µmol·kg·−1h−1 (mean ± SEM) during 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 µmol·kg·−1h−1), and comparable to those reported in healthy newborns. During convalescence total urinary nitrate excreted increased by 66% (p < 0.05), urinary15NO3 increased from 0.29 ± 0.07 to 0.74 ± 0.15 µmol·d−1 (p < 0.05), and the rate of plasma arginine conversion to NO increased from 10.3 ± 2.2 to 45.6 ± 13 µmol·d−1 (p < 0.05). This study indicates a decreased plasma arginine utilization for whole body NO synthesis during the acute vasoconstrictive state of PPHN and suggests that arginine availability may become an important factor in NO formation.

Original languageEnglish (US)
Pages (from-to)17-24
Number of pages8
JournalPediatric Research
Issue number1
StatePublished - Jul 1995
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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