Prostacyclin enhances stretch-induced surfactant secretion in alveolar epithelial type II cells

Inhalative vasodilator therapy, employing gaseous nitric oxide (NO) or aero solized prostaglandin PCI, is of interest for regional pulmonary vasodilati on in ARDS and pulmonary hypertension. We investigated the impact of the NO donor spermine NONOate as well as PGFl(2) and its stable chemical analog i loprost on cultured rat alveolar epithelial type II cell (ATII) surfactant secretion. The NO donor provoked a significant increase in the ATII cGMP co ntent, further enhanced by type V phosphodiesterase (PDE) inhibition, but a ffected neither baseline nor mechanical stretch-induced surfactant secretio n. The prostanoids caused a marked increase in the epithelial cAMP content, further amplified by coadministration of type III/IV PDE inhibitors. Basel ine surfactant secretion was not altered by this approach, but mechanical s tretch-induced liberation of surfactant was significantly increased, most p rominently in the ATII with the highest cAMP levels due to the presence of both iloprost and PDE III/IV inhibitors. In contrast, epithelial phosphoino sitide metabolism, well responsive to purinergic stimulation as positive co ntrol, was unchanged in prostanoid-exposed cells. We conclude that the PGl( 2)-cAMP axis, but not the NO-cCMP axis, forwards a markedly enhanced secret ory response to the physiological stimulus of cell surface stretching, whic h may be relevant for therapeutic use of these agents.