Effects of zaprinast on renal nerve stimulation-induced anti-natriuresis in anaesthetized dogs

1. We examined whether zaprinast, a putative cGMP-specific phosphodiesteras e inhibitor, affects neural control of renal function in pentobarbital-anae sthetized dogs. 2. Renal nerve stimulation (1 Hz, 1 ms duration) reduced urine flow rate, u rinary Na+ excretion (UNaV) and fractional excretion of Na+ (FENa) with lit tle change in either renal blood flow (RBF) or glomerular filtration rate ( GFR). 3. Intrarenal arterial infusion of zaprinast (10 and 100 mu g/kg per min) i ncreased basal urine how rate, UNaV and FENa but not RBF or GFR, Zaprinast infusion (100 mu g/kg per min) also increased renal venous plasma cGMP conc entration and urinary cGMP excretion. 4. Renal nerve stimulation-induced reductions in UNaV and FENa were attenua ted during zaprinast infusion, whereas the reduction in urine how rate was resistant to zaprinast. 5. Renal nerve stimulation increased the renal venous plasma noradrenaline concentration and renal noradrenaline efflux, which remained unaffected dur ing infusion of zaprinast (100 mu g/kg per min). 6. The results of the present study suggest that zaprinast induces natriure sis and counteracts adrenergically induced anti-natriuresis by acting on re nal tubular sites in the dog kidney in viva.