Modulation of hemorheological parameters by the erythrocyte redox thiol status

Clin Hemorheol Microcirc. 2008;40(2):99-111.

Abstract

Background: There is growing knowledge about the association between hemorheological blood disorders and compromised microcirculation in erythrocyte abnormalities. Effects of the non-neuronal cholinergic elements, especially acetylcholinesterase, on the erythrocyte hemorheological parameters were characterized in the past. However, alterations of these parameters have not been studied under the influence of the cellular redox thiol status.

Methods: Aliquots of venous blood from ten healthy male subjects were incubated in vitro with increasing concentrations of a thiol reducer agent (dithiothreitol 1, 10, 50 microM final concentrations) in the presence and absence of acetylcholinesterase substrate (acetylcholine) or inhibitor (velnacrine maleate). The following parameters were determined in all blood samples aliquots: erythrocyte aggregation, erythrocyte deformability and lipid membrane fluidity. Blood smears were performed.

Results: Dithiothreitol induces no significant changes on the hemorheological behaviour of human red cells. Upon intracellular thiol stimulation, the presence of AChE effectors (either acetylcholine or velnacrine) decreases erythrocyte aggregation and elongation indexes.

Conclusion: The addition of DTT to blood samples aliquots, contributing to the redox thiol status, is not directly involved in the modulation of erythrocyte rheological properties. However, upon acetylcholinesterase modulation by its substrate or inhibitor, changes on the hemorheological parameters are triggered by DTT. Associated pharmacological interest is considerable to address the hemorheology-hemostasis-microcirculation triad disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology*
  • Acetylcholinesterase / metabolism
  • Cholinergic Agents / pharmacology*
  • Cholinesterase Inhibitors / pharmacology*
  • Dithiothreitol / pharmacology*
  • Erythrocyte Aggregation / drug effects*
  • Erythrocyte Deformability / drug effects*
  • Erythrocytes / cytology
  • Erythrocytes / metabolism*
  • Hematologic Diseases / metabolism
  • Humans
  • Male
  • Membrane Fluidity / drug effects*
  • Microcirculation
  • Oxidation-Reduction / drug effects
  • Tacrine / analogs & derivatives*
  • Tacrine / pharmacology

Substances

  • Cholinergic Agents
  • Cholinesterase Inhibitors
  • Tacrine
  • Acetylcholinesterase
  • Acetylcholine
  • Dithiothreitol
  • velnacrine