Ontogeny of Atrial Natriuretic Peptide and Its Receptor In the Lung: Effects on Perinatal Surfactant Release

Abstract

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 Ϫ10 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 cGMPdependent 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. (Pediatr Res 63: 239-244, 2008)

Influence of Exercise on Airway Epithelia in Cystic Fibrosis

“…Natriuretic receptors have been identified in the epithelia of the bronchioles and Type I/II alveolar cells (20). ANP signals epithelial cells via basolateral natriuretic peptide receptor A, causing changes in G proteins, and an increase in intracellular cyclic guanosine 3',5'-monophosphate (56).…”

“…ANP signals epithelial cells via basolateral natriuretic peptide receptor A, causing changes in G proteins, and an increase in intracellular cyclic guanosine 3',5'-monophosphate (56). Activation of the natriuretic peptide receptor inhibits apical sodium absorption in the kidneys and intestines (68) and inhibits ENaC in Type II alveolar cells (20). Olivera et al (59) reported that when pulmonic circulation pressure was kept constant, the perfusion of ANP increased epithehal permeability and reduced Na^ absorption in isolated rat lung.…”

Natriuretic peptide C receptor in the developing sheep lung: role in perinatal transition

“…All protocols were approved by the Institutional Animal Care and Use Committee (IACUC) of the State University of New York at Buffalo. The technique utilized for the isolation and culture of ATIIs has been characterized in detail previously by our laboratory and is outlined briefly (5). For fetal lambs (136 days of gestation, full term is 145 days), pregnant ewes were anesthetized by an intravenous injection of pentobarbital sodium (2.3 mg/kg) and placed under isoflurane (1.5%) general anesthesia.…”

“…We previously reported that both ANP and its primary receptor, NPR-A, are highly expressed in ATIIs in the fetal lung before birth, but that shortly after birth this expression disappears (5). ANP at 10 − 10 M stimulated surfactant secretion in fetal and newborn sheep ATIIs.…”

Atrial Natriuretic Peptide presence in parotid gland of human fetus at 13th week of development and in adult man

“…The literature data on the ANP-ontogeny refer to heart [13][14][15], brain [16][17][18], and lung [19]. The morphology of developing salivary glands was described in rat [20,21], mouse [22], miniature pig [23], and in humans [24].…”