The purpose of this study was to test the hypothesis that circulating red blood cells (RBCs) release
adenosine deaminase (ADA) when injured. This hypothesis was evaluated in rats using
dimethyl sulfoxide (
DMSO) to damage RBCs. Boluses and infusions of
DMSO caused a reduction in urinary
adenosine and a concomitant
hemoglobinuria, and the ability of
DMSO to reduce urinary
adenosine was blocked by pretreatment with the ADA inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine. Infusions of
DMSO also significantly enhanced ADA activity in urine and plasma. Dimethylsulfone, an analog of
DMSO that does not affect RBCs, did not cause
hemoglobinuria and did not affect urinary
adenosine. High concentrations of
DMSO did not affect
adenosine metabolism in rat kidneys perfused without RBCs, and
DMSO did not decrease urinary
adenosine in rats rendered severely anemic (hematocrit < 15%) by replacing whole blood with plasma. However,
DMSO did decrease urinary
adenosine in rats without a spleen, a major source of
adenosine deaminase apart from circulating RBCs.
DMSO reduced renal interstitial levels of
adenosine and attenuated bradycardic responses to exogenous
adenosine, and these effects were prevented by erythro-9-(2-hydroxy-3-nonyl)adenine. These results indicate that circulating damaged RBCs release significant amounts of ADA, a process that may predispose to vasoocclusive events.