Adenosine and renal sodium handling: direct natriuresis and renal nerve-mediated antinatriuresis

Adenosine infusion is associated with natriuresis as well as antinatriuresis. The physiologic significance of these opposite effects is unknown but may have to do with different conditions of ischemia, in which adenosine accumulates. These effects were characterized in the rat. First, intrarenal and systemic infusions within one animal were performed. Infusing 10 micrograms/min into the left renal artery increased sodium by approximately 50%; however, the subsequent infusion of 50 micrograms/min into the thoracic aorta decreased sodium excretion by approximately 60%, in association with a small reduction of blood pressure. Second, to explore the effect of intrarenal adenosine in tubular sodium handling, free-flow micropuncture experiments were performed. The intrarenal infusion of 10 micrograms/min again caused sodium excretion, but no change in GFR, volume, and sodium deliveries up to the early distal tubule was found. Apparently, the direct effect of adenosine in the kidney is sodium excretion, by a tubular action beyond the early distal tubule. Third, to further characterize the indirect effect, which apparently is sodium retention, adenosine was infused systemically at low rates, in order to avoid a decrease in blood pressure. A 25 micrograms/min infusion again caused sodium retention, in the absence of a fall in blood pressure. After acute left renal denervation, the antinatriuretic effect disappeared in the denervated kidney but remained in the right kidney. These data suggest that increased intrarenal adenosine suppresses sodium reabsorption at some distal nephron site, appropriately decreasing the workload of the kidney. On the other hand, systemic adenosine stimulates sodium reabsorption, an effect that is appropriate to improve systemic circulation and depends on the renal nerves.