title: Transient neonatal high oxygen exposure leads to early adult cardiac dysfunction, remodeling, and activation of the renin-angiotensin system.
abstract: Perinatal conditions (such as preterm birth) can affect adult health and disease, particularly the cardiovascular system. Transient neonatal high O(2) exposure in rat in adulthood (a model of preterm birth-related complications) leads to elevated blood pressure, vascular rigidity, and dysfunction with renin-angiotensin system activation. We postulate that neonatal hyperoxic stress also affects myocardial structure, function, and expression of renin-angiotensin system components. Sprague-Dawley pups were kept with their mother in 80% O(2) or in room air (control) from days 3 to 10 of life. Left ventricular function was assessed in 4-, 7-, 12-week-old (echocardiography) and in 16-week-old (intraventricular catheterization) male O(2)-exposed versus control rats. At 16 weeks, hearts from O(2)-exposed rats showed cardiomyocyte hypertrophy, enhanced fibrosis, and increased expression of transforming growth factor-β1, senescence-associated proteins p53 and Rb, upregulation of angiotensin II type 1 (AT1) receptor expression (protein and AT1a/b mRNA), and downregulation of AT2 receptors. At 4 weeks (before blood pressure increase), the expression of cardiomyocyte surface area, fibrosis, p53, and AT1b was significantly increased and AT2 decreased in O(2)-exposed animals. After 4 weeks of continuous angiotensin II infusion (starting at 12 weeks), O(2)-exposed rats developed severe heart failure, with impaired myocardial mechanical properties compared with saline-infused rats. Transient neonatal O(2) exposure in rats leads to left ventricular hypertrophy, fibrosis and dysfunction, and increased susceptibility to heart failure under pressure overload. These results are relevant to the growing population of individuals born preterm who may be at higher risk of cardiac dysfunction when faced with increased peripheral resistance associated with hypertension, vascular diseases, and aging.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Sainte-Justine University Hospital Research Center, 3175, Chemin de la Côte-Sainte-Catherine, H3T 1C5, Montreal, Quebec, Canada. anne-monique.nuyt@recherche-ste-justine.qc.ca.
authors.forename: Mariane
authors.initials: M
authors.lastname: Bertagnolli
authors.forename: Fanny
authors.initials: F
authors.lastname: Huyard
authors.forename: Anik
authors.initials: A
authors.lastname: Cloutier
authors.forename: Zackary
authors.initials: Z
authors.lastname: Anstey
authors.forename: Julie-Émilie
authors.initials: JÉ
authors.lastname: Huot-Marchand
authors.forename: Catherine
authors.initials: C
authors.lastname: Fallaha
authors.forename: Pierre
authors.initials: P
authors.lastname: Paradis
authors.forename: Ernesto L
authors.initials: EL
authors.lastname: Schiffrin
authors.forename: Denis
authors.initials: D
authors.lastname: Deblois
authors.forename: Anne Monique
authors.initials: AM
authors.lastname: Nuyt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006331:Heart Diseases / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D010100:Oxygen
keywords: angiotensin II receptors; endomyocardial fibrosis; heart failure; oxidative stress; preterm birth; senescence