Renal handling and production of plasma and urinary adenosine

The present study was undertaken to determine the renal handling of plasma adenosine and the relative contribution of the kidney to the adenosine in the renal venous plasma and urine. Injections of radiolabeled adenosine, as a tracer of arterial adenosine, along with reference compounds (either inulin or 9-beta-D-arabinofuranosyl hypoxanthine, an analogue of adenosine that does not occupy the nucleoside carrier) were coupled with measurements of endogenous adenosine in the arterial and renal venous plasma and urine of 11 anesthetized dogs. The arterial and venous concentration of endogenous adenosine was 60 +/- 16 and 52 +/- 10 nM, respectively. Urinary adenosine concentration was 312 +/- 53 nM and the fractional excretion was 0.71 +/- 0.14. Of the radiolabeled adenosine injected into the renal artery, approximately 53 +/- 3% of the filtered tracer was recovered in the urine, and only 11 +/- 1% of the tracer was recovered in the venous plasma. These results demonstrate uptake of adenosine from both the tubular and vascular compartments, and analysis of single-injection multiple-indicator curves indicates that a substantial amount of the extracted arterial adenosine enters and remains in cells. We conclude that arterial plasma contributes significantly to adenosine excreted in the urine but only minimally to renal venous adenosine. Furthermore, any intervention that alters cellular uptake and metabolism of adenosine may lead to significant changes in extracellular adenosine.