Measurement of NO synthesis in humans by L-[N-152]arginine: Application to the response to vaccination

D C Macallan, L M Smith, J Ferber, Eric Milne, G E Griffin, N Benjamin, M A McNurlan

    Research output: Contribution to journalArticle

    Abstract

    Induction of nitric oxide (NO) synthesis is a key element of the inflammatory response in humans. We describe a sensitive gas isotope ratio mass spectrometric (GIRMS) method for measuring urinary [N-15]nitrate production during intravenous infusion of L-[guanidino-N-15(2)]arginine and its application to investigate the effects of a controlled inflammatory stimulus, typhoid vaccination, on NO synthesis in humans. Intravenous infusion of L-[N-15(2)]arginine at 5-12 mu mol . kg(-1) . h(-1) for 24 h in three subjects was used to determine arginine and nitrate pool kinetics. Eight subjects received primed constant infusion of 2.5 mu mol . kg(-1) . h(-1) of L-[N-15(2)]arginine for 12 h once before and again after typhoid vaccination. NO synthesis was calculated from N-15 enrichment of plasma arginine and urinary nitrate, measured by gas chromotography mass spetrometry and GIRMS, respectively and total urinary nitrate excretion. Baseline NO synthesis was 298 +/- 44 nmol . h(-1) . kg lean body mass(-1), representing 0.41% of arginine flux. After vaccination, NO synthesis (267 +/- 77 nmol . h(-1) . kg(-1)) was not increased (P = 0.18), despite demonstration of an acute phase response. Typhoid vaccination is not accompanied by accelerated NO synthesis.

    Original languageEnglish
    Pages (from-to)R1888-R1896
    Number of pages9
    JournalAmerican Journal of Physiology-Regulatory Integrative and Comparative Physiology
    Volume272
    Issue number6
    Publication statusPublished - Jun 1997

    Keywords

    • nitrate
    • acute phase response
    • inflammation
    • nitric-oxide pathway
    • urinary nitrate excretion
    • L-arginine
    • plasma arginine
    • adult man
    • kinetics
    • sepsis
    • diet

    Cite this

    Macallan, D. C., Smith, L. M., Ferber, J., Milne, E., Griffin, G. E., Benjamin, N., & McNurlan, M. A. (1997). Measurement of NO synthesis in humans by L-[N-152]arginine: Application to the response to vaccination. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 272(6), R1888-R1896.

    Measurement of NO synthesis in humans by L-[N-152]arginine: Application to the response to vaccination. / Macallan, D C ; Smith, L M ; Ferber, J ; Milne, Eric; Griffin, G E ; Benjamin, N ; McNurlan, M A .

    In: American Journal of Physiology-Regulatory Integrative and Comparative Physiology, Vol. 272, No. 6, 06.1997, p. R1888-R1896.

    Research output: Contribution to journalArticle

    Macallan, DC, Smith, LM, Ferber, J, Milne, E, Griffin, GE, Benjamin, N & McNurlan, MA 1997, 'Measurement of NO synthesis in humans by L-[N-152]arginine: Application to the response to vaccination', American Journal of Physiology-Regulatory Integrative and Comparative Physiology, vol. 272, no. 6, pp. R1888-R1896.
    Macallan, D C ; Smith, L M ; Ferber, J ; Milne, Eric ; Griffin, G E ; Benjamin, N ; McNurlan, M A . / Measurement of NO synthesis in humans by L-[N-152]arginine: Application to the response to vaccination. In: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. 1997 ; Vol. 272, No. 6. pp. R1888-R1896.
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    AU - Ferber, J

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    AU - Griffin, G E

    AU - Benjamin, N

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    AB - Induction of nitric oxide (NO) synthesis is a key element of the inflammatory response in humans. We describe a sensitive gas isotope ratio mass spectrometric (GIRMS) method for measuring urinary [N-15]nitrate production during intravenous infusion of L-[guanidino-N-15(2)]arginine and its application to investigate the effects of a controlled inflammatory stimulus, typhoid vaccination, on NO synthesis in humans. Intravenous infusion of L-[N-15(2)]arginine at 5-12 mu mol . kg(-1) . h(-1) for 24 h in three subjects was used to determine arginine and nitrate pool kinetics. Eight subjects received primed constant infusion of 2.5 mu mol . kg(-1) . h(-1) of L-[N-15(2)]arginine for 12 h once before and again after typhoid vaccination. NO synthesis was calculated from N-15 enrichment of plasma arginine and urinary nitrate, measured by gas chromotography mass spetrometry and GIRMS, respectively and total urinary nitrate excretion. Baseline NO synthesis was 298 +/- 44 nmol . h(-1) . kg lean body mass(-1), representing 0.41% of arginine flux. After vaccination, NO synthesis (267 +/- 77 nmol . h(-1) . kg(-1)) was not increased (P = 0.18), despite demonstration of an acute phase response. Typhoid vaccination is not accompanied by accelerated NO synthesis.

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