Am. J. Respir. Crit. Care Med., Volume 160, Number 3, September 1999, 846-851

Prostacyclin Enhances Stretch-induced Surfactant Secretion in Alveolar Epithelial Type II Cells

FRANK ROSE, KLAUS ZWICK, HOSSEIN ARDESCHIR GHOFRANI, ULF SIBELIUS, WERNER SEEGER, DIETER WALMRATH, and FRIEDRICH GRIMMINGER

Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany

Inhalative vasodilator therapy, employing gaseous nitric oxide (NO) or aerosolized prostaglandin PGI₂, is of interest for regional pulmonary vasodilation in ARDS and pulmonary hypertension. We investigated the impact of the NO donor spermine NONOate as well as PGI₂ and its stable chemical analog iloprost on cultured rat alveolar epithelial type II cell (ATII) surfactant secretion. The NO donor provoked a significant increase in the ATII cGMP content, further enhanced by type V phosphodiesterase (PDE) inhibition, but affected neither baseline nor mechanical stretch-induced surfactant secretion. The prostanoids caused a marked increase in the epithelial cAMP content, further amplified by coadministration of type III/IV PDE inhibitors. Baseline surfactant secretion was not altered by this approach, but mechanical stretch-induced liberation of surfactant was significantly increased, most prominently in the ATII with the highest cAMP levels due to the presence of both iloprost and PDE III/IV inhibitors. In contrast, epithelial phosphoinositide metabolism, well responsive to purinergic stimulation as positive control, was unchanged in prostanoid-exposed cells. We conclude that the PGI₂-cAMP axis, but not the NO-cGMP axis, forwards a markedly enhanced secretory response to the physiological stimulus of cell surface stretching, which may be relevant for therapeutic use of these agents.

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