The effects of P2X receptor agonists on renal sodium and water excretion in anaesthetized rats

Aim: To investigate in vivo effects of P2X receptor activation on sodium and water excretion in urine. Methods: The clearance experiments were carried out in anaesthetized rats during intravenous infusion (2 mu mol kg-1 + 20 nmol (kg min)-1, v = 40 mu L min-1) of P2X receptors agonists: alpha,beta-methylene ATP (alpha,beta-meATP) and beta,gamma-methylene ATP (beta,gamma-meATP). Cortical blood flow (CBF) was estimated by laser Doppler flux during intrarenal artery infusion of beta,gamma-meATP (20 nmol (kg min)-1, v = 2 mu L min-1). Influence of alpha,beta-meATP and beta,gamma-meATP on the activity of Na-K-ATPase was investigated in isolated proximal tubules. Results: Intravenous infusion of beta,gamma-meATP resulted in a marked, progressively increasing diuresis and this effect was accompanied by a progressive increase in the sodium excretion rate. The glomerular filtration rate was unaffected. The effects of beta,gamma-meATP were abolished by P2 receptor antagonist PPADS (70 nmol (kg min)-1). CBF increased by 16 +/- 2% during renal artery infusion of beta,gamma-meATP. Furthermore, alpha,beta-meATP and beta,gamma-meATP increased 1.5-fold lithium clearance (C-Li). Sodium excretion, expressed as a fraction of the distal delivery (CNaCLi-1), increased 1.5-fold during infusion of alpha,beta-meATP or beta,gamma-meATP. Both agonists at 10-6 m produced a statistical significant decrement in the ouabain-sensitive ATPase activity about 16-20% and these effects were blocked in the presence of PPADS. Conclusion: Activation of P2X receptors increased renal sodium and water excretion. Mechanistically, P2X agonists increased renal perfusion and inhibited sodium reabsorption via an Na-K-ATPase-dependent mechanism.