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

Toshihiro Sekizawa, Yuichiro Shima, Kozo Yoshida, Masayuki Tanahashi, Makoto Yoshida, Mizue Suzuki-Kusaba, Hiroaki Hisa, Susumu Satoh

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

1. We examined whether zaprinast, a putative cGMP-specific phosphodiesterase inhibitor, affects neural control of renal function in pentobarbital-anaesthetized dogs. 2. Renal nerve stimulation (1 Hz, 1 ms duration) reduced urine flow rate, urinary Na+ excretion (UNaV) and fractional excretion of Na+ (FENa) with little change in either renal blood flow (RBF) or glomerular filtration rate (GFR). 3. Intrarenal arterial infusion of zaprinast (10 and 100 μg/kg per min) increased basal urine flow rate, UNaV and FENa but not RBF or GFR. Zaprinast infusion (100 μg/kg per min) also increased renal venous plasma cGMP concentration and urinary cGMP excretion. 4. Renal nerve stimulation-induced reductions in UNaV and FENa were attenuated during zaprinast infusion, whereas the reduction in urine flow rate was resistant to zaprinast. 5. Renal nerve stimulation increased the renal venous plasma noradrenaline concentration and renal noradrenaline efflux, which remained unaffected during infusion of zaprinast (100 μg/kg per min). 6. The results of the present study suggest that zaprinast induces natriuresis and counteracts adrenergically induced antinatriuresis by acting on renal tubular sites in the dog kidney in vivo.

Original languageEnglish
Pages (from-to)1008-1012
Number of pages5
JournalClinical and Experimental Pharmacology and Physiology
Volume25
Issue number12
DOIs
Publication statusPublished - 1998 Jan 1

Keywords

  • CGMP-specific phosphodiesterase
  • Dog
  • Noradrenaline release
  • Renal nerves
  • Urinary Na excretion
  • Zaprinast

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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