Abstract
Background/Aims: P<sup>1</sup>,P<sup>4</sup>-diadenosine tetraphosphate (Ap<sub>4</sub>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<sub>4</sub>A. Methods: We evaluated the tubular sites of Ap<sub>4</sub>A action using the lithium clearance technique. Results: Ap<sub>4</sub>A at a priming dose of 2 µmol/kg with subsequent infusion at 20 nmol/kg/min increased fractional water and sodium excretion 2.5- and 5.6-fold, respectively. Moreover, Ap<sub>4</sub>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<sub>4</sub>A. Conclusion: These results suggest that Ap<sub>4</sub>A induces natriuresis mainly through inhibition of proximal tubular reabsorption of sodium.
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