Adenosine effects on renal function in the rat: role of sodium intake and cytochrome P450

Nephron Physiol. 2013;123(1-2):1-5. doi: 10.1159/000353705. Epub 2013 Jul 25.

Abstract

Background/aims: Adenosine (ADO) causes vasodilation in most tissues. In the kidney it can induce vasoconstriction or vasodilation, depending on the prevailing stimulation of A1 or A2 receptors (A1R, A2R). ADO-induced alterations of renal excretion may be secondary to haemodynamic changes, or reflect a direct influence on tubular transport. This whole-kidney study explored renal excretory responses to ADO receptor stimulation as related to renal haemodynamics sodium intake and cytochrome P450 (CYP-450) activity.

Methods: The effects of ADO or an A2aR agonist (DPMA) on urine flow (V), sodium excretion (UNaV) and total solute excretion were examined in anaesthetized Wistar rats on a low-sodium or high-sodium (HS) diet. Total renal blood flow (RBF; renal artery probe), and outer- and inner-medullary blood flows (OM-BF, IM-BF; laser-Doppler fluxes) were also determined.

Results: Consistent opposed effects of ADO and DPMA were only observed with the HS diet. ADO increased V (150%) and UNaV (100%); there were also significant increases in RBF, OM-BF and IM-BF. These changes were prevented by 1-aminobenzotriazol, a CYP-450 inhibitor. In HS rats, DPMA significantly decreased arterial blood pressure and renal excretion.

Conclusions: Post-ADO diuresis/natriuresis was in part secondary to renal hyperperfusion; the response was probably mediated by CYP-450-dependent active agents. Selective A2aR stimulation induced systemic vasodilation, major hypotension, and a secondary decrease in renal excretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology*
  • Adenosine A2 Receptor Agonists / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cytochrome P-450 Enzyme System / metabolism*
  • Diuresis / drug effects
  • Kidney / drug effects*
  • Kidney / physiology*
  • Male
  • Natriuresis / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P1 / metabolism
  • Renal Circulation / drug effects
  • Renal Circulation / physiology
  • Sodium / urine*
  • Sodium, Dietary / administration & dosage

Substances

  • Adenosine A2 Receptor Agonists
  • Receptors, Purinergic P1
  • Sodium, Dietary
  • CGS 24012
  • Cytochrome P-450 Enzyme System
  • Sodium
  • Adenosine