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.
Conclusion:
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.
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Acknowledgements
A.C. performed experimental procedures, analyzed and interpreted data, and drafted the manuscript. D.G. contributed to study conception and design, analyzed and interpreted data, and finalized the manuscript. R.C. performed experimental procedures, analyzed and interpreted data. Y.W. contributed to study conception and design, performed experimental procedures; analyzed and interpreted data, and finalized the manuscript.
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Chu, A., Gozal, D., Cortese, R. et al. Cardiovascular dysfunction in adult mice following postnatal intermittent hypoxia. Pediatr Res 77, 425–433 (2015). https://doi.org/10.1038/pr.2014.197
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DOI: https://doi.org/10.1038/pr.2014.197
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