HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/H3038    most recent 01238.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Rozier, M. D. Articles by Ellsworth, M. L. Search for Related Content PubMed PubMed Citation Articles by Rozier, M. D. Articles by Ellsworth, M. L.

Lactate interferes with ATP release from red blood cells

Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, Missouri

Submitted 10 November 2006 ; accepted in final form 9 February 2007

Upon exposure to low PO₂, 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 PO₂, 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 PO₂. 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 PO₂. 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.

vascular control; microcirculation; adenosine 5'-triphosphate; erythrocytes; lactate dichloroacetate

This article has been cited by other articles:

				S. P. Mortensen, R. Damsgaard, E. A. Dawson, N. H. Secher, and J. Gonzalez-Alonso Restrictions in systemic and locomotor skeletal muscle perfusion, oxygen supply and VO2 during high-intensity whole-body exercise in humans J. Physiol., May 15, 2008; 586(10): 2621 - 2635. [Abstract] [Full Text] [PDF]