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 influences renal functions in anesthetized dogs. The intrarenal arterial infusion of rolipram (0.1, 0.3, and 1 microgram/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 microgram/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.
Tanahashi
M
M
Department of Pharmacology, Pharmaceutical Institute, Tohoku University, Aobayama, Sendai, Japan.
Hara
S
S
Yoshida
M
M
Suzuki-Kusaba
M
M
Hisa
H
H
Satoh
S
S
D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood* / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects*; D020889:Rolipram; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D015363:Quinolones; C021294:cilostamide; D012964:Sodium; D000242:Cyclic AMP; D020889:Rolipram; D007213:Indomethacin