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

The present study was undertaken to examine whether phosphodiesterases III and IV regulate renal cAMP level and whether inhibition of these enzymes in fluences renal functions in anesthetized dogs. The intrarenal arterial infu sion of rolipram (0.1, 0.3, and 1 mu g/kg/min), a selective phosphodiestera se IV inhibitor, increased renal blood flow, glomerular filtration rate, ur ine flow rate, and urinary Na+ excretion with elevating arterial and renal venous plasma cAMP concentrations and urinary cAMP excretion. However, cilo stamide (0.1, 0.3, and 1 mu g/kg/min), a selective phosphodiesterase III in hibitor, 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, r educed the basal arterial and renal venous plasma cAMP concentrations and b lunted the rolipram-induced elevation of cAMP concentrations and urinary cA MP excretion. The effects of rolipram on renal hemodynamics and urine forma tion were attenuated in the presence of indomethacin. These results suggest that in the dog kidney in vivo, 1) phosphodiesterase IV, but not phosphodi esterase Ill, participates in degradation of cAMP and 2) the inhibition of phosphodiesterase IV enhances glomerular filtration and urinary Na+ excreti on, the responses of which depend in part on indomethacin-susceptible (pros taglandin-mediated, probably) control of basal cAMP level.