title: Lactate interferes with ATP release from red blood cells.
abstract: Upon exposure to low Po(2), the red blood cells of most species, including humans, release increased amounts of ATP that ultimately serves as a regulator of vascular tone matching oxygen supply with demand. In pathological conditions such as malaria and sepsis, a maldistribution of perfusion exists with its severity often correlated with the extent of elevation of serum lactate frequently in the absence of an alteration in pH. We hypothesized that the increased levels of lactate might impair the ability of red blood cells to appropriately respond to conditions of low Po(2), thus preventing its important blood flow regulatory role. Using an in vitro system and rabbit red blood cells, we evaluated the capacity of cells incubated with lactate to release increased amounts of ATP in response to acute exposure to low Po(2). We found that in the presence of lactate, the red blood cells did not release ATP. However, when sodium dichloroacetate, a drug used clinically to lower blood lactate levels, was added, ATP release was restored to levels that were not different from that of control cells (no lactate), even though intracellular levels of ATP were not. These results support the presence of a distinct flow regulatory pool of ATP within the red blood cell that can be independently regulated, and that lactate interferes with the ATP production within this pool, thereby diminishing the amount of ATP available for release on exposure to low Po(2). Therefore, if lactate levels can be reduced, the vascular regulatory capacity of the red blood cell should be restored, thus enabling the appropriate matching of oxygen supply with oxygen demand.
authors.affiliation: Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rozier
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Zata
authors.forename: Mary L
authors.initials: ML
authors.lastname: Ellsworth
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D011817:Rabbits
chemical_list: D019344:Lactic Acid; D000255:Adenosine Triphosphate; D003999:Dichloroacetic Acid; D010100:Oxygen