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Related Experiment Videos

eNOS function is developmentally regulated: uncoupling of eNOS occurs postnatally.

Eugenia Mata-Greenwood1, Chrystal Jenkins, Kathryn N Farrow

  • 1Dept. of Pediatrics, Northwestern Univ., Ward 12-191, 303 E. Chicago Ave., Chicago, IL 60611-008, USA.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|September 7, 2005
PubMed
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Newborn pulmonary arteries adapt to breathing by altering endothelial nitric oxide synthase (eNOS) function, shifting from producing only nitric oxide (NO) to generating superoxide alongside NO after birth.

Area of Science:

  • Cardiovascular Physiology
  • Pulmonary Vascular Biology
  • Neonatal Adaptation

Background:

  • Transition to air breathing at birth requires functional endothelial vasoactive agents.
  • Endothelial nitric oxide synthase (eNOS) plays a critical role in regulating pulmonary vascular tone.

Purpose of the Study:

  • To investigate the developmental changes in eNOS function in ovine pulmonary artery (PA) vessels and endothelial cells from fetal to young postnatal life.
  • To determine the mechanisms underlying altered eNOS activity and associated reactive oxygen species production postnatally.

Main Methods:

  • Vessel relaxation studies using NOS activators and inhibitors in fetal and 4-week-old sheep PA.
  • Measurement of nitric oxide (NO) and superoxide production in isolated PA endothelial cells (PAEC) under various stimulation conditions (A-23187, VEGF, laminar shear stress).

Related Experiment Videos

  • Analysis of eNOS phosphorylation, cofactor levels (biopterin), and protein interactions (HSP90).

    • Main Results:

    • Postnatal PA vessels showed enhanced relaxation to NOS activation compared to fetal vessels.
    • Fetal PAEC produced only NO upon eNOS stimulation, while 4-week-old PAEC produced both NO and superoxide.
    • Tetrahydrobiopterin (BH4) precursor supplementation normalized NO production and abolished superoxide generation in 4-week-old PAEC.

    Conclusions:

    • Postnatal pulmonary vascular adaptation involves a functional uncoupling of eNOS, leading to increased superoxide production.
    • Altered biopterin levels may contribute to eNOS uncoupling and the shift in vasoactive agent production after birth.
    • These findings highlight a developmental shift in pulmonary vascular signaling crucial for adapting to extrauterine life.