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EFFECTS OF ZAPRINAST ON RENAL NERVE STIMULATION‐INDUCED ANTI‐NATRIURESIS IN ANAESTHETIZED DOGS
Author(s) -
Sekizawa Toshihiro,
Shima Yuichiro,
Yoshida Kozo,
Tanahashi Masayuki,
Yoshida Makoto,
SuzukiKusaba Mizue,
Hisa Hiroaki,
Satoh Susumu
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02175.x
Subject(s) - zaprinast , renal blood flow , renal function , endocrinology , medicine , urine flow rate , natriuresis , chemistry , kidney , renal circulation , nitric oxide , guanylate cyclase
SUMMARY 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 (1Hz, 1ms 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 anti‐natriuresis by acting on renal tubular sites in the dog kidney in vivo.