Accumulation of an endogenous inhibitor of nitric oxide synthase during graded hemorrhagic shock

A. Aneman*, V. Backman, J. Snygg, C. Von Bothmer, L. Fandriks, A. Pettersson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Asymmetric dimethylarginine (ADMA) represents an endogenous inhibitor of nitric oxide (NO) production. THe production of ADMA has been shown to increase during cellular stress, e.g., hypoxia. Furthermore, ADMA has recently been reported to accumulate in plasma during terminal renal failure as a consequence of diminished urinary excretion. Since tissue hypoxia and oliguria are both characteristics of severe hemorrhagic shock, this study was performed in order to establish whether plasma concentrations of ADMA increase during hemorrhagic shock. Six pigs were subjected to graded hemorrhage (20% and 40% of the calculated blood volume), resulting in significant (P < 0.05) reductions in blood pressure and cardiac output (from 98 ± 4 to 36 ± 5 mm Hg and from 3.0 ± 0.2 to 1.4 ± 0.2 L/min, respectively). Plasma ADMA concentrations as determined by high-performance liquid chromatography (HPLC) increased from a pre-hemorrhage value of 3.4 ± 0.3 μM to 3.9 ± 0.4 μM (ns) and 5.2 ± 0.4 μM (P < 0.05), respectively. The present study demonstrates that plasma ADMA concentrations increase significantly during hemorrhagic shock. Thus, inhibition of the arginine- nitric oxide pathway as a result of ADMA accumulation, may represent an additional physiological mechanism to maintain systemic blood pressure in response to acute hypovolemia.

Original languageEnglish
Pages (from-to)111-114
Number of pages4
JournalCirculatory Shock
Issue number3
Publication statusPublished - 1994


  • dimethylarginine
  • nitric oxide-antagonists and inhibitors
  • shock-hemorrhage


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