Mechanisms regulating cAMP-mediated growth of bovine neonatal pulmonary artery smooth muscle cells

Neonatal pulmonary artery smooth muscle cells (PASMCs) exhibit enhanced gro wth capacity and increased growth responses to mitogenic stimuli compared w ith adult PASMCs. Because intracellular signals mediating enhanced growth r esponses in neonatal PASMCs are incompletely understood, we questioned whet her 1) G(q) agonists increase cAMP content and 2) increased cAMP is proprol iferative. Endothelin-l and angiotensin Il increased both cAMP content and proliferation in neonatal but not in adult PASMCs. Inhibition of protein ki nase C and protein kinase A activity nearly eliminated the endothelin-1- an d angiotensin II-induced growth of neonatal PASMCs. Moreover, cAMP increase d proliferation in neonatal but not in adult cells. Protein kinase C-stimul ated adenylyl cyclase was expressed in both cell types, suggesting that ins ensitivity to stimulation of cAMP in adult cells was not due to decreased e nzyme expression. Our data collectively indicate that protein kinase C stim ulation of cAMP is a critical signal mediating proliferation of neonatal PA SMCs that is absent in adult PASMCs and therefore may contribute to the uni que proproliferative phenotype of these neonatal cells.