Effects of rolipram and cilostamide on renal functions and cyclic AMP release in anesthetized dogs

Masayuki Tanahashi, Sunao Hara, Makoto Yoshida, Mizue Suzuki-Kusaba, Hiroaki Hisa, Susumu Satoh

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

The present study was undertaken to examine whether phosphodiesterases III and IV regulate renal cAMP level and whether inhibition of these enzymes influences renal functions in anesthetized dogs. The intrarenal arterial infusion of rolipram (0.1, 0.3, and 1 μg/kg/min), a selective phosphodiesterase IV inhibitor, increased renal blood flow, glomerular filtration rate, urine flow rate, and urinary Na+ excretion with elevating arterial and renal venous plasma cAMP concentrations and urinary cAMP excretion. However, cilostamide (0.1, 0.3, and 1 μg/kg/min), a selective phosphodiesterase III inhibitor, did not affect the values of these parameters. Indomethacin (3 mg/kg i.v. bolus and 1 mg/kg/min i.v. infusion), a cyclooxygenase inhibitor, reduced the basal arterial and renal venous plasma cAMP concentrations and blunted the rolipram-induced elevation of cAMP concentrations and urinary cAMP excretion. The effects of rolipram on renal hemodynamics and urine formation were attenuated in the presence of indomethacin. These results suggest that in the dog kidney in vivo, 1) phosphodiesterase IV, but not phosphodiesterase III, participates in degradation of cAMP and 2) the inhibition of phosphodiesterase IV enhances glomerular filtration and urinary Na+ excretion, the responses of which depend in part on indomethacin-susceptible (prostaglandin-mediated, probably) control of basal cAMP level.

Original languageEnglish
Pages (from-to)1533-1538
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume289
Issue number3
Publication statusPublished - 1999 Jun 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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