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 cruci al mediator in the regulation of pulmonary vascular resistance (PVR) a nd 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 messeng er RNA (mRNA) in ovine and mouse lung during perinatal development. We report that within 1 h following birth, PDES activity, protein, and m RNA levels decrease in both species, in a manner that correlates with known decreases in PVR in early transition. However, from 4 to 7 d fol lowing 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 i mply that PDE5 may be an important mediator in the regulation of PVR i n normal and possibly in pathologic states, and may ultimately provide a basis for PDE5 inhibitors as a treatment for pulmonary hypertension .