Developmental changes in HIF transcription factor in carotid body: Relevance for O2 sensing by chemoreceptors

Abstract

Before birth, the peripheral chemoreceptors located in the carotid bodies (CB) are adapted to the low fetal PO2 and are relatively insensitive to hypoxia. After birth, the sensitivity of the CB to hypoxia is reset in response to the rise in PO2. The mechanism underlying this resetting, which requires several days to complete, remains unknown. We have investigated the possibility that the hypoxia-inducible factors HIF-1α and HIF-2α, which are activated by oxygen deprivation, are involved in this resetting process. Accordingly, we used immunostaining and densitometry to quantitate the levels of the HIF-1α and HIF-2α proteins in the rat CB during early perinatal life and after exposure to in vivo hypoxia during adolescence. Tyrosine hydroxylase (TH) was used as a marker for catecholaminergic neurons and oxygen-sensitive cells in the CB. Double-immunostaining revealed constitutive expression of HIF-1α in both glomus cells (TH+) and sustentacular cells (TH-) of the CB of adolescent rats. However, immunoreactivity toward HIF-2α was restricted to glomus cells. After exposure to hypoxia (8% O2, 6 h), the expression of HIF-1α was selectively upregulated in glomus cells and apparent translocation of both HIF-1α and HIF-2α to the nucleus was observed. Both of these proteins were expressed constitutively in the CB during the perinatal transition period. During the first postnatal week, the intensity of immunostaining for HIF-1α in glomus cells decreased markedly, whereas the level of HIF-2α remained constant. We suggest that this selective down-regulation of HIF-1α may be involved in the postnatal maturation of CB responsiveness to hypoxia. Copyright © 2005 International Pediatric Research Foundation, Inc.