Phosphodiesterase 3 activity is reduced in dog lung following pacing-induced heart failure.
We hypothesized that decreases in expression and/or activity of cAMP-specific phosphodiesterases (PDE) contribute to protective adaptations observed in lung after heart failure. In this study, we compared PDE activity in lung parenchyma isolated from control dogs and those paced to heart failure by assaying cyclic nucleotide hydrolysis in fractions of homogenate supernatant eluted from DEAE-Trisacryl columns. Cyclic nucleotide hydrolysis due to PDE3, PDE4, and PDE5 isoforms was predominant in both control and paced groups. The ratio of PDE3 activity to total cAMP PDE activity was decreased in the paced group compared with control (P < 0.05), whereas PDE4 or PDE5 activity ratios were not different between the two groups. With the use of RT-PCR, message expression for PDE3A or PDE3B did not differ between the two groups. Cilostamide, a selective PDE3 inhibitor, and forskolin, a nonspecific agonist for adenylyl cyclase, both inhibited thapsigargin-induced increases in endothelial permeability in control lung. We conclude that PDE3 activity, but not mRNA expression, is reduced in lung from dogs paced to heart failure, a change that could contribute to heart failure-induced attenuation of the lung endothelial permeability response to injury.
Tarpey
Siobhán B
SB
Department of Physiology, University of South Alabama, Mobile, Alabama 36688, USA.
Sawmiller
Darrell R
DR
Kelly
Claire
C
Thompson
W Joseph
WJ
Townsley
Mary I
MI
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002196:Capillaries / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004285:Dogs; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006868:Hydrolysis; D008168:Lung / Q000201:enzymology*; D010138:Pacemaker, Artificial; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000502:physiology; D015363:Quinolones / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010726:Phosphodiesterase Inhibitors; D015363:Quinolones; D005576:Colforsin; C021294:cilostamide; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D006152:Cyclic GMP