Renal haemodynamics and natriuretic responses to intravenous administration of diadenosine tetraphosphate (Ap4A) and nicotinamide adenine dinucleotide (NAD) in rat

Effects of Ap4A and NAD - precursor of adenosine, on renal plasma flow (RPF), glomerular filtration rate (GFR) and urine excretion were determined in the anaesthetised rats. Infusion of Ap4A or NAD (i.v., bolus - 1 mumol/kg followed by 10 nmol/min/kg) decreased RPF and GFR (by 30 and 40%, respectively). In spite of GFR reduction during Ap4A infusion, the significant increase in sodium excretion and urine flow was noticed: fractional sodium (FENa) and urine excretion (FEurine) rose 15-fold and 2.5-fold in comparision with the control value, respectively. In contrast to Ap4A, NAD-induced decrease in GFR was associated with parallel decrease in sodium and urine excretion, thus the FENa and FEurine did not significantly change. Pretreatment with adenosine deaminase (adenosine degrading enzyme, 2 U/min/kg) or theophylline (P1-receptors antagonist, 0.2 mmol/min/kg) ceased responses to NAD, wherease Ap4A-induced changes were not affected. Pre-treatment with suramin (P2-receptors antagonist, (i.v., bolus - 12 mg/kg followed by 1.2 mg/min/kg)) completely abolished the renal effects of Ap4A. We conclude that Ap4A may exert specific action on renal function. It acts different from NAD that modified renal function through its hydrolysis product - adenosine. Ap4A might reduce glomerular filtration rate and evoke natriuresis and diuresis, and its effects are probably mediated through stimulation of P2-receptors.