Lactate interferes with ATP release from red blood cells

Area of Science:

• Physiology
• Biochemistry
• Pathology

Background:

• Red blood cells release adenosine triphosphate (ATP) in response to low oxygen (Po2) to regulate vascular tone.
• Pathological conditions like sepsis and malaria involve impaired blood flow and elevated serum lactate.
• The role of lactate in modulating red blood cell ATP release and its impact on oxygen delivery is unclear.

Purpose of the Study:

• To investigate whether elevated lactate levels impair red blood cell ATP release under hypoxic conditions.
• To determine if reducing lactate levels can restore the blood flow regulatory function of red blood cells.

Main Methods:

• An in vitro system using rabbit red blood cells was employed.
• Cells were incubated with lactate to simulate pathological conditions.
• Adenosine triphosphate (ATP) release in response to low Po2 was measured.
• The effect of sodium dichloroacetate, a lactate-lowering drug, on ATP release was assessed.

Main Results:

• Lactate significantly inhibited the release of ATP from red blood cells exposed to low Po2.
• Intracellular ATP levels were not affected by lactate.
• Addition of sodium dichloroacetate restored ATP release to normal levels, despite unchanged intracellular ATP.
• A distinct, regulated pool of ATP within red blood cells appears to be targeted by lactate.

Conclusions:

• Lactate interferes with the production or availability of ATP in a specific pool within red blood cells, impairing their ability to regulate blood flow.
• Reducing lactate levels may restore the vascular regulatory capacity of red blood cells.
• This finding suggests a potential therapeutic strategy for conditions with maldistributed perfusion by targeting lactate reduction.