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 μmol kg(-1) + 20 nmol (kg min)(-1) , v = 40 μL min(-1)) of P2X receptors agonists: α,β-methylene ATP (α,β-meATP) and β,γ-methylene ATP (β,γ-meATP). Cortical blood flow (CBF) was estimated by laser Doppler flux during intrarenal artery infusion of β,γ-meATP (20 nmol (kg min)(-1) , v = 2 μL min(-1)). Influence of α,β-meATP and β,γ-meATP on the activity of Na-K-ATPase was investigated in isolated proximal tubules.
Results: Intravenous infusion of β,γ-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 β,γ-meATP were abolished by P2 receptor antagonist PPADS (70 nmol (kg min)(-1)). CBF increased by 16 ± 2% during renal artery infusion of β,γ-meATP. Furthermore, α,β-meATP and β,γ-meATP increased 1.5-fold lithium clearance (C(Li)). Sodium excretion, expressed as a fraction of the distal delivery (C(Na) C(Li) (-1)), increased 1.5-fold during infusion of α,β-meATP or β,γ-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.
© 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.