Impaired ventilatory responses to hypoxia in mice deficient in endothelin-converting-enzyme-1

S. Renolleau, S. Dauger, G. Vardon, B. Levacher, M. Simonneau, M. Yanagisawa, C. Gaultier, J. Gallego

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34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)705-712
Number of pages8
JournalPediatric Research
Volume49
Issue number5
DOIs
StatePublished - Jan 1 2001

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ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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Renolleau, S., Dauger, S., Vardon, G., Levacher, B., Simonneau, M., Yanagisawa, M., Gaultier, C., & Gallego, J. (2001). Impaired ventilatory responses to hypoxia in mice deficient in endothelin-converting-enzyme-1. Pediatric Research, 49(5), 705-712. https://doi.org/10.1203/00006450-200105000-00016