Annals of Hematology

, Volume 92, Issue 4, pp 505–508 | Cite as

Effect of chronic elevated asymmetric dimethylarginine (ADMA) levels on granulopoiesis

  • Gernot Beutel
  • Ronny Perthel
  • Mayuren Suntharalingam
  • Stefanie M. Bode-Böger
  • Jens Martens-Lobenhoffer
  • Jan T. Kielstein
  • Heike Kielstein
Original Article

Abstract

The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is elevated in both animal models of chronic inflammatory disorders as well as in patients with chronic inflammatory disease. In vivo data suggest that ADMA can increase the number of circulating monocytes and possibly affect their adhesion potential in vitro. The aim of our study was to evaluate possible effects of chronically elevated levels of ADMA on white blood cell count (WBC), leukocyte subsets, and WBC distribution pattern using a model of chronic exogenous ADMA infusion. Male Sprague–Dawley rats (n = 20, 10 weeks of age) were randomized to receive either (1) isotonic saline or (2) ADMA applied by osmotic mini pumps. After 28 days of infusion, all animals were sacrificed for blood and tissue sampling. WBC count, flow cytometry for subtype assessment, and histological assessment were performed. Over a time period of 28 days, continuous ADMA infusion significantly increased mean plasma levels (1.26 ± 0.07 μmol/l) as compared to saline infusion (0.57 ± 0.02 μmol/l). Clinical side effects were not observed. Despite a physiologically relevant rise in ADMA plasma levels, measured by decrease of the l-arginine/AMDA ratio—a surrogate parameter of NO production capacity—there was no effect on WBC count or pattern of leukocyte subsets. Numbers and morphology of peripheral blood cells as well as number of NK-cells leveling liver and spleen were not affected by chronic ADMA infusion. Chronically elevated ADMA levels in otherwise healthy rats did not affect WBC counts or leukocyte subsets. Furthermore, anemia frequently found in patients with progressive renal failure and elevated ADMA levels, was not observed. In a chronic inflammatory state, elevated ADMA levels themselves are rather the result than the cause of the underlying inflammatory process.

Keywords

Asymmetric dimethylarginine ADMA Peripheral blood count Granulopoiesis Lymphocytes subsets 

Notes

Acknowledgment

This study is supported by a grant of the Werner Jackstädt Stiftung to JTK and HK.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Gernot Beutel
    • 1
  • Ronny Perthel
    • 2
  • Mayuren Suntharalingam
    • 4
  • Stefanie M. Bode-Böger
    • 3
  • Jens Martens-Lobenhoffer
    • 3
  • Jan T. Kielstein
    • 4
  • Heike Kielstein
    • 2
  1. 1.Department of Hematology, Hemostasis, Oncology, and Stem Cell TransplantationHannover Medical SchoolHannoverGermany
  2. 2.Department of Anatomy and Cell BiologyFaculty of Medicine, Martin Luther University Halle-WittenbergHalleGermany
  3. 3.Institute of Clinical PharmacologyHospital of the Otto-von-Guericke-University of MagdeburgMagdeburgGermany
  4. 4.Department of Nephrology and HypertensionMedical School HannoverHannoverGermany

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