Effects of ATP on rat renal haemodynamics and excretion: role of sodium intake, nitric oxide and cytochrome P450

Aim: Adenosine-5'-triphosphate (ATP) affects intrarenal vascular tone and tubular transport via P2 receptors; however, the actual role of the system in regulation of renal perfusion and excretion remains unclear and is the subject of this whole-kidney study. Methods: Effects of suprarenal aortic ATP infusion, 0.6-1.2 mg kg(-1) h(-1), were examined in anaesthetised rats maintained on low- (LS) or high-sodium (HS) diet. Renal artery blood flow (RBF, transonic flow probe) and the perfusion (laser-Doppler flux) of the superficial cortex (CBF) and outer and inner medulla (OM-BF, IM-BF) were measured, together with sodium and water excretion and urine osmolality. Results: Adenosine-5'-triphosphate did not change arterial pressure, RBF or CBF while the effects on medullary perfusion depended on sodium intake. In LS rats ATP increased IM-BF 19 +/- 6%, the effect was prevented by inhibition of nitric oxide (NO) with N-nitro-L-arginine methyl ester. In HS rats ATP decreased OM-BF 16 +/- 3% and IM-BF (7 +/- 4%, not significant); previous inhibition of cytochrome P450 with 1-aminobenzotriazol blunted the OM-BF decrease and reversed the previous decrease of IM-BF to a 13 +/- 8% increase. Inhibition of P2 receptors with pyridoxal derivative (PPADS) abolished medullary vascular responses to ATP. In HS rats pre-treated with PPADS, ATP increased tubular reabsorption, probably via adenosine formation and stimulation of P1 receptors. Conclusion: The data indicate a potential role of ATP in the selective control of renal medullary perfusion, different in sodium depleted and sodium replete rats. The action of ATP appears to be mediated by the NO system and the cytochrome P450 dependent vasoactive metabolites.