Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message

During transitional circulation, the pulmonary vascular bed undergoes a rapid and profound reduction in both tone and vascular smooth-muscle (VSM) content. 3',5'-Guanylate cyclic monophosphate (cGMP) is a crucial mediator in the regulation of pulmonary vascular resistance (PVR) and VSM pro...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 1998-07, Vol.158 (1), p.279-288
Main Authors: HANSON, K. A, BURNS, F, RYBALKIN, S. D, MILLER, J. W, BEAVO, J, CLARKE, W. R
Format: Article
Language:English
Subjects:
3',5'-Cyclic-GMP Phosphodiesterases
Aging - physiology
Animals
Animals, Newborn
Biological and medical sciences
Cyclic GMP - analysis
Cyclic Nucleotide Phosphodiesterases, Type 5
Fundamental and applied biological sciences. Psychology
Hemodynamics. Rheology
Hydrolysis
Immunoblotting
Lung - enzymology
Lung - metabolism
Mice
Mice, Inbred C57BL
Muscle, Smooth, Vascular - chemistry
Phosphoric Diester Hydrolases - metabolism
Polymerase Chain Reaction
Pulmonary Circulation - physiology
RNA, Messenger - analysis
Sheep
Vertebrates: cardiovascular system
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Summary:During transitional circulation, the pulmonary vascular bed undergoes a rapid and profound reduction in both tone and vascular smooth-muscle (VSM) content. 3',5'-Guanylate cyclic monophosphate (cGMP) is a crucial mediator in the regulation of pulmonary vascular resistance (PVR) and VSM proliferation. Hydrolysis of cGMP is achieved predominately by cGMP-specific phosphodiesterases (PDEs). Among the cGMP-specific PDEs, PDE5 is quantitatively prevalent in lung tissue. We have investigated the levels of pulmonary PDE5 enzymatic activity, protein, and messenger RNA (mRNA) in ovine and mouse lung during perinatal development. We report that within 1 h following birth, PDE5 activity, protein, and mRNA levels decrease in both species, in a manner that correlates with known decreases in PVR in early transition. However, from 4 to 7 d following birth, a secondary increase in PDE5 activity, protein, and mRNA occurs in both ovine and mouse lung, suggesting a complex regulation of PVR and VSM proliferation in late perinatal development. Our data imply that PDE5 may be an important mediator in the regulation of PVR in normal and possibly in pathologic states, and may ultimately provide a basis for PDE5 inhibitors as a treatment for pulmonary hypertension.
ISSN:1073-449X
1535-4970
DOI:10.1164/ajrccm.158.1.9711042