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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 μg/kg/min), a selective phosphodiesteras...
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Published in: | The Journal of pharmacology and experimental therapeutics 1999-06, Vol.289 (3), p.1533-1538 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 0022-3565 1521-0103 |