Stretch-related changes in lung cAMP after partial pneumonectomy

Abstract

In rats, left pneumonectomy (PNX) initiates rapid compensatory hyperplastic growth of the right lung. Previous work indicated that increased polyamine uptake associated with post-PNX distortion or "stretch" of the remaining tissue and altered adenosine 3',5'-cyclic monophosphate (cAMP) metabolism may play a role in the early phase of the growth response. Evidence was sought to link these observations with the goal of understanding control of compensatory growth. At day 1 or 3 after left PNX in vivo, increased right lung cAMP was associated with activation of the cAMP-dependent protein kinase (PKa). Total PKa activity was unaffected, but the PKa activity ratio (-cAMP/+cAMP) doubled, providing evidence for PNX-associated activation of the kinase in vivo. Neither cAMP nor PKa was altered in sham-operated control lungs. To determine whether increased distension of the right lung after PNX might initiate these changes, lungs of unoperated animals were perfused 40 min in vitro, either without ventilation or with a distending constant positive airway pressure (CPAP) of 20 cmH2O. CPAP rapidly increased uptake of the polyamine spermidine (SPD; 1.5 microM), tissue cAMP, and the PKa activity ratio, in a manner similar to that observed after PNX. Both tissue cAMP and the kinase activity ratio increased with 1 microM forskolin (FSK), as expected, but SPD uptake was unaffected by FSK. FSK did not diminish the CPAP-associated elevations of SPD uptake (P less than 0.01) or cAMP (P less than 0.05), but the kinase was not further activated by CPAP with FSK present.(ABSTRACT TRUNCATED AT 250 WORDS)