Abstract
Endothelin-converting-enzyme (ECE-1) catalyzes the proteolytic activation of big endothelin-1 to mature endothelin-1. Most homozygous ECE-1−/− embryos die in utero and show severe craniofacial, enteric, and cardiac malformations precluding ventilatory function assessment. In contrast, heterozygous ECE-1+/− embryos develop normally. Their respiratory function at birth has not been studied. Taking into account previous respiratory investigations in mice with endothelin-1 gene disruption, we hypothesized that ECE-1-deficient mice may have impaired ventilatory control. We analyzed ventilatory responses to hypercapnia (8% CO2) and hypoxia (10% O2) in newborn and adult mice heterozygous for ECE-1 deficiency (ECE-1+/−) and in their wild-type littermates (ECE-1+/+). Ventilation, breath duration, and tidal volume were measured using whole-body plethysmography. Ventilatory responses to hypoxia were significantly weaker in ECE-1+/− than in ECE-1+/+ newborn mice (percentage ventilation increase: 1 ± 25%versus 33 ± 29%, p = 0.010). Baseline breathing variables and ventilatory responses to hypercapnia were normal in the ECE-1+/− newborn mice. No differences were observed between adult ECE-1+/− and ECE-1+/+ mice. We conclude that ECE-1 is required for normal ventilatory response to hypoxia at birth.
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Abbreviations
- CCHS:
-
congenital central hypoventilation syndrome
- ECE-1:
-
endothelin-converting-enzyme-1
- ET-1:
-
endothelin-1
- GDNF:
-
glial-cell-line-derived neurotrophic factor
- HSCR:
-
Hirschsprung’s disease
- NTS:
-
nucleus tractus solitarius
- RET:
-
rearranged during transfection
- TTOT:
-
breath duration
- VE:
-
ventilation
- VT:
-
tidal volume
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Supported by Fondation Pour La Recherche Médicale (grant awarded to S.R.) and by Université Paris VII (Legs Poix).
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Renolleau, S., Dauger, S., Vardon, G. et al. Impaired Ventilatory Responses to Hypoxia in Mice Deficient in Endothelin-Converting-Enzyme-1. Pediatr Res 49, 705–712 (2001). https://doi.org/10.1203/00006450-200105000-00016
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DOI: https://doi.org/10.1203/00006450-200105000-00016
