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

Abstract:

:During the transition at birth to air breathing, regulation of surfactant release from alveolar type II (ATII) cells is critical. Atrial natriuretic peptide (ANP) stimulates natriuretic peptide receptor-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 inhibition significantly blocked this release. We conclude that ANP stimulates 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 speculate that increased activity of the ANP/NPR-A pathway in late gestation may prime the surfactant system, preparing the lung for air breathing.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

D'Angelis CA,Holm BA,Lakshminrusimha S,Nickerson PA,Swartz DD,Sokolowski J,Nielsen LC,Ryan RM

doi

10.1203/PDR.0b013e318163a215

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

239-44

issue

3

eissn

0031-3998

issn

1530-0447

pii

00006450-200803000-00005

journal_volume

63

pub_type

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