Background and purpose: The kidney receives very dense innervations of adrenergic nerves affecting renal haemodynamics and tubular function. ATP has been established as a cotransmitter and as neuromodulator molecule in sympathetic nerves. This purinergic signaling involves P2 receptors, which are structurally and functionally divided into ion channels (P2X_1-7) and metabotropic receptors (P2Y_{1,2,4,6,11-14}). The adrenergic and purinergic transmission may affect each other which, in turn, may modify renal function. The aim of the present study was to investigate whether renal denervation modulates the results of activation of P2X receptors.

Experimental approach: The clearance experiments in anaesthetized Wistar rats were performed 7 days after bilateral denervation of the kidneys. The changes in glomerular filtration rate (GFR), renal plasma flow (RPF), sodium and water excretion in urine were investigated during systemic infusion (i.v., 2 µmol/kg +20 nmol/kg^/min) of β,g-methylene ATP (β,g-meATP), the poorly hydrolysable ATP analogue - P2X receptors agonist with greatest potency at P2X₁ receptor. For the purpose of qualifications of the possible changes in the level of P2X₁ receptor in denervated kidney we examined, by RT-PCR, the mRNA level for P2X₁.

Key results: The infusion of β,g-meATP increased RPF and fractional sodium excretion from proximal and distal nephron segments without significant changes in fractional water excretion from distal nephron segments in control group (sham-operated, n=5). The chronic renal denervation (n=6) produced several times greater β,g-meATP-induced diuresis and natriuresis than in control group. The mean arterial pressure and GFR remained unchanged in both group during β,g-meATP infusion. The RT-PCR experiments showed increased expression of P2X₁ receptor with relation to reference gene b-actin (0.24±0.02 vs 0.08±0.04).

Conclusions and implications: Our results indicate that renal chronic denervation leads to hypersensitivity to β,g-meATP, which may be due to, at least in part, increased expression of P2X₁ receptors.

Acknowledgments: The study was supported by the Polish National Committee for Scientific Research, grant no. 3 P05A 07225.

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