P-1, P-4-diadenosine tetraphosphate (Ap(4)A) inhibits proximal tubular reabsorption of sodium in rats

Background/Aims: P-1,P-4-diadenosine tetraphosphate (Ap(4)A) is a vasoactive dinucleotide possessing natriuretic activity. It is unclear, however, which part of the nephron is the target site of action for Ap(4)A. Methods: We evaluated the tubular sites of Ap(4)A action using the lithium clearance technique. Results: Ap(4)A at a priming dose of 2 mu mol/kg with subsequent infusion at 20 nmol/kg/min increased fractional water and sodium excretion 2.5- and 5.6-fold, respectively. Moreover, Ap(4)A increased lithium clearance 1.9-fold and fractional lithium excretion 2.8-fold. Fractional water and sodium excretion from distal nephron segments was not significantly affected by Ap(4)A. Conclusion: These results suggest that Ap(4)A induces natriuresis mainly through inhibition of proximal tubular reabsorption of sodium. Copyright (c) 2007 S. Karger AG, Basel