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

• Published in: Japanese Journal of Pharmacology 1999, Vol.79 (suppl.1), p.36-36
• Main Authors: Tanahashi, Masayuki, Hara, Sunao, Saitoh, Kazutomo, Hisa, Hiroaki, Satoh, Susumu
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)34166-6

The present study was undertaken to examine whether phosphodiesterase (PDE) III and PDE 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 PDE IV inhibitor, increased renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (UV) and urinary Na^+ excretion (UNaV) with elevating arterial and renal venous plasma cAMP concentrations and urinary cAMP excretion. The intrarenal arterial infusion of cilostamide (0.1, 0.3 and 1 μg/kg/min), a selective PDE III inhibitor, did not affect the values of these parameters. However, the infusion of cilostamide increased GFR, UV, UNaV and fractional Na^+ excretion in the presence of a nitric oxide synthase inhibitor L-NAME (5 or 50 μg/kg/ min, i.a.). These results suggest that in the dog kidney in vivo 1) PDE IV participates in degradation of cAMP, 2) the inhibition of PDE IV enhances urinary Na^+ and water excretion mainly by increasing glomerular filtration and 3) PDE III can also participate in cAMP degradation, but its activity is inhibited by the nitric oxide-cGMP system.