title: Cardiovascular dysfunction in adult mice following postnatal intermittent hypoxia.
abstract: BACKGROUND
  Ex-premature infants are at higher risk for hypertension and cardiovascular disease as adults, although the mechanisms underlying such increased risks are unknown. We hypothesize that postnatal exposure to intermittent hypoxia (IH) leads to cardiovascular dysfunction in adulthood with alterations of the renin-angiotensin pathway.
  
  
  METHODS
  Neonatal mice were exposed to IH for 4 wk. At the age of 3 mo, various cardiovascular measurements were obtained.
  
  
  RESULTS
  IH-exposed mice exhibited higher systolic blood pressure, impaired baroreflex responses, and decreased heart rate variability. Furthermore, IH-exposed mice manifested evidence of endothelial dysfunction, as shown by reduced reperfusion indices after tail vessel occlusion and impaired vasodilatory responses to acetylcholine. CD31(+) endothelial cells isolated from mesenteric arteries of IH-exposed mice expressed higher levels of angiotensin-converting enzyme and reactive oxygen species; plasma angiotensin-II levels were also significantly higher in these animals. In addition, DNA methylation patterns of the Ace1 and the Agt genes in these cells were congruent with their expression patterns.
  
  
  CONCLUSIONS
  Our results suggest that exposures to postnatal IH alter the normal development of the renin-angiotensin system and promote the occurrence of cardiovascular dysfunction during adulthood in mice.
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, Illinois.
authors.forename: Alison
authors.initials: A
authors.lastname: Chu
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, Illinois.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, Illinois.
authors.forename: Rene
authors.initials: R
authors.lastname: Cortese
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, Illinois.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000804:Angiotensin II / Q000097:blood; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D017704:Baroreflex; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology*; D019175:DNA Methylation; D006339:Heart Rate; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: C534932:Agt protein, mouse; D000808:Angiotensinogen; D000804:Angiotensin II