Effects of Rolipram and Cilostamide on Renal Functions and Cyclic AMP Release in Anesthetized Dogs1

The present study was undertaken to examine whether phos-phodiesterases III and IV regulate renal cAMP level and whether inhibition of these enzymes influences renal functions in anes-thetized dogs. The intrarenal arterial infusion of rolipram (0.1, 0.3, and 1 mg/kg/min), a selective phosphodiesterase IV inhib-itor, increased renal blood flow, glomerular filtration rate, urine flow rate, and urinary Na1 excretion with elevating arterial and renal venous plasma cAMP concentrations and urinary cAMP excretion. However, cilostamide (0.1, 0.3, and 1 mg/kg/min), a selective phosphodiesterase III inhibitor, did not affect the val-ues 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 concentra-tions and blunted the rolipram-induced elevation of cAMP con-centrations 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 phospho-diesterase III, participates in degradation of cAMP and 2) the inhibition of phosphodiesterase IV enhances glomerular filtra-tion and urinary Na1 excretion, the responses of which depend in part on indomethacin-susceptible (prostaglandin-mediated, probably) control of basal cAMP level. cAMP has been suggested to participate in the control of renal functions. It is well known that cAMP derivatives in-crease renal blood flow (Higashio et al., 1980), enhance glo-merular filtration (Okahara et al., 1977), and cause diuresis (Robinson and Mirkovitch, 1980). Intracellular cAMP level is regulated by phosphodiesterase (PDE). PDEs have been classified into at least seven isozym