Effects of diadenosine polyphosphates on renal function and blood pressure in anesthetized Wistar rats

Abstract

In this study, the effects of diadenosine polyphosphates on kidney function were examined. Intravenous application of diadenosine hexaphosphate (AP6A) led to a significant threefold increase in both urine flow (from 2.45 ± 0.2 to 13.8 ± 0.74 μL/min per 100 g body wt (P < 0.05]) and Na+ excretion (from 0.41 ± 0.12 to 1.52 ± 0.28 μmol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). In contrast, diadenosine triphosphate dose- dependently reduced urine flow (from 3.74 ± 0.3 to 2.57 ± 0.1 μL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.45 ± 0.1 to 0.13 ± 0.1 μmol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). ATP and the P(2y) purinoceptor agonist γ-S-ATP did not significantly modulate urine flow and Na+ excretion. α,β-methylene-ATP, a P(2x) purinoceptor agonist, significantly increased urine flow from 1.74 ± 0.5 to 4.07 ± 1.51 μL/min per 100 g body wt, whereas Na+ excretion was unaffected. The effects were independent of alterations in GFR. Pretreatment with indomethacin (2.0 mg/kg body wt iv) completely abolished the effects of AP6A on urine flow and Na+ excretion. Similarly, pretreatment with the endothelin antagonist bosentan abolished the effects of AP6A on both urine flow and Na+ excretion, whereas suramin had no effects on the AP6A-induced increase in urine flow. In conclusion, diadenosine polyphosphates exert specific actions on urine flow and Na+ excretion that are different from the effects of ATP. AP6A may partially influence renal function by stimulating prostaglandin and endothelin release.