Ontogeny of atrial natriuretic peptide and its receptor in the lung: effects on perinatal surfactant release.

During the transition at birth to air breathing, regula- tion of surfactant release from alveolar type II (ATII) cells is critical. Atrial natriuretic peptide (ANP) stimulates natriuretic peptide recep- tor-A (NPR-A) and increases intracellular cGMP. We examined the changes in ANP and NPR-A in respiratory epithelium during the perinatal period using immunohistochemistry and studied the effect of ANP on surfactant release from ATII cells isolated from fetal and newborn lambs. NPR-A mRNA was detected in the fetal lung by Northern Blot and RT-PCR. At 100 d gestation (term 145 d), ANP staining was absent and NPR-A staining was weak in cuboidal epithelial cells. ANP and NPR-A staining was prominent in ATII cells at 136 d gestation and was undetectable postnatally. ANP stimulated (maximal effect at 10 10 M) surfactant release from both late gestation fetal and neonatal ATII cells. Protein kinase G inhibi- tion significantly blocked this release. We conclude that ANP stim- ulates surfactant release in isolated perinatal ATII cells by a cGMP- dependent mechanism. ANP and NPR-A expression in ATII cells is greatest in late gestation and declines sharply postnatally. We spec- ulate that increased activity of the ANP/NPR-A pathway in late gestation may prime the surfactant system, preparing the lung for air breathing. (Pediatr Res 63: 239-244, 2008)