Perinatal hypoxia causes ventricular enlargement associated with increased atrial natriuretic peptide (ANP) mRNA levels in newborn mice

A. Roger Hohimer, Matt Mysliwiec, Kathryn Lee, Lowell E. Davis, George A. Pantely

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

We sought to examine both the short-term and residual effects of perinatal hypoxia on ventricular mass and function of mice. We postulated that the magnitude of the ventricular hypertrophy would be determined by the timing of the exposure, be linked to augmented atrial natriuretic peptide (ANP) expression, and would persist to young adulthood. Furthermore, mice deficient in the ANP receptor type A (ANPRA) would have even greater hypertrophy. Newborns were placed in a 12% oxygen (O2) chamber either shortly after birth or at 8 days of age. Controls were raised in room air. After 8 or 16 days, pups were terminated and the right ventricle (RV) and left ventricle including the septum (LVS) were excised and weighed and total RNA was extracted. Hypoxia caused a reduction in body weight (BW) with an increase in right ventricle (RV) weight, rendering an increased RV to BW ratio and increased LVS/BW, albeit less. Hypertrophy was most pronounced in pups exposed to hypoxia in the first days of extrauterine life. A rapid postnatal decline in both RV and LVS ANP mRNA levels was observed in control animals, while the hypoxia elevated ANP mRNA. In mice missing the ANPRA, both ventricles were more massive than in wild type and hypoxia further augmented RV/BW and LVS/BW. In normal adult animals returned to room air after 16 days of hypoxia, RV but not LVS hypertrophy persisted in both sexes; there was an interaction between gender and the perinatal hypoxic stress on LVS dimension and perhaps on contractility. Thus perinatal hypoxia may "program" the adult mouse heart and vasculature.

Original languageEnglish (US)
Pages (from-to)241-254
Number of pages14
JournalHigh Altitude Medicine and Biology
Volume4
Issue number2
DOIs
StatePublished - Jan 1 2003

Keywords

  • Cardiac
  • Echocardiography
  • Gender
  • Hypertrophy
  • Hypoxic pulmonary vasoconstriction

ASJC Scopus subject areas

  • Physiology
  • Public Health, Environmental and Occupational Health

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