[HTML][HTML] Endothelin-1 mediates hypoxia-induced increases in vascular collagen in the newborn mouse lung

N Ambalavanan, P Li, A Bulger, J Murphy-Ullrich… - Pediatric …, 2007 - nature.com
Pediatric research, 2007nature.com
Abstract Endothelin-1 (ET-1) mediates hypoxia-mediated pulmonary vascular remodeling
(HPVR), and endothelin-A receptor (ET-AR) blockade prevents HPVR in newborn mice. Our
objective was to determine postnatal effects of chronic hypoxia and/or ET-AR blockade on
lung ET-1, ET-AR, ET-BR, and vascular collagen and elastin. Newborn C57BL/6 mice (n= 6–
8/gp) given either BQ610 (ET-AR blocker) or vehicle were exposed to air or hypoxia (12% O
2) from birth for 1, 3, or 14 d. Lung ET-1 was assessed by ELISA, and ET-AR and ET-BR by …
Abstract
Endothelin-1 (ET-1) mediates hypoxia-mediated pulmonary vascular remodeling (HPVR), and endothelin-A receptor (ET-AR) blockade prevents HPVR in newborn mice. Our objective was to determine postnatal effects of chronic hypoxia and/or ET-AR blockade on lung ET-1, ET-AR, ET-BR, and vascular collagen and elastin. Newborn C57BL/6 mice (n= 6–8/gp) given either BQ610 (ET-AR blocker) or vehicle were exposed to air or hypoxia (12% O 2) from birth for 1, 3, or 14 d. Lung ET-1 was assessed by ELISA, and ET-AR and ET-BR by immunohistochemistry. Vascular collagen and elastin were assessed by quantitative image analysis. ET-1, ET-AR, ET-BR, collagen I and III, and tropoelastin mRNA levels were assessed by real-time quantitative RT-PCR. We observed that: 1) hypoxia attenuated the normal postnatal decrease in ET-1 and collagen content; 2) ET-AR blockade reduced collagen independent of O 2; 3) hypoxia increased elastin mRNA expression and attenuated the normal postnatal decrease in elastin content; and 4) BQ610 reduced elastin mRNA but not elastin content. We conclude that, in neonatal mice, hypoxia attenuates normal postnatal decreases in ET-1, vascular collagen, and elastin. ET-AR blockade reduces collagen fiber area but not mRNA, and does not decrease elastin despite reducing its expression.
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