Cardiovascular dysfunction in adult mice following postnatal intermittent hypoxia

Abstract

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.

Early postnatal exposure to intermittent hypoxia in rodents is proinflammatory, impairs white matter integrity, and alters brain metabolism

“…The long term physiological effects of IH during the neonatal period have been studied extensively in rodent models (8–10), but few studies have focused on brain development and/or injury, or on brain inflammation. However, two studies in mice have indicated that early postnatal exposure to relatively mild IH report biochemical and electron microscopy evidence for a decrease in myelination possibly due to impaired myelinogenesis, impaired axonal maturation, short and long term neuro-functional deficits and electrophysiological changes that may form the basis for more long-term neurobehavioral sequelae (11, 12).…”

Sleep Apnoea and Early Antecedents of Adult Disease

“…Furthermore, the IH-exposed mice also exhibited impaired vasodilatory responses to acetylcholine, and endothelial cells that were harvested from their mesenteric arteries expressed higher levels of angiotensin-converting enzyme (ACE) and reactive oxygen species, along with elevated plasma angiotensin-II (AGT) levels. Furthermore, increased DNA methylation patterns of the ACE1 and the AGT genes were apparent in the endothelial cells of the IH-exposed mice 113 .…”

“…It is now well established that premature birth, and possibly the presence of apnoea of prematurity, are accompanied by an increased risk of cardiovascular and metabolic disease during adulthood [110][111][112] . To further examine the viability of the epigenetic hypothesis, we exposed neonatal mice to IH, and then allowed them to recover in normoxia till they reached adulthood 113 . IH-exposed mice manifested evidence of endothelial dysfunction, as shown by reduced reperfusion indices after tail vessel occlusion indicating abnormal flow mediated vasodilation.…”

The Perinatal Origins of Cardiovascular Disease

“…22,23 A study 24 using a mouse model of postnatal chronic intermittent hypoxia demonstrated persistent elevated systolic blood pressure, impaired baroreflex, decreased heart Elevated glucocorticoid levels have been associated with increased blood pressure.…”

“…24 These studies suggest that for a premature infant, postnatal exposures may be as important as prenatal environment for the programming of cardiovascular disease. There is a desperate need for more research in this area to identify modifiable exposures in neonatal intensive care to optimize long-term outcomes in these patients.…”