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Am J Physiol Lung Cell Mol Physiol. 2015 Nov 15;309(10):L1186-98. doi: 10.1152/ajplung.00044.2015. Epub 2015 Sep 4.

Maternal-pup interaction disturbances induce long-lasting changes in the newborn rat pulmonary vasculature.

Author information

1
Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; and.
2
Department of Paediatrics and Physiology, University of Toronto, Toronto, Ontario, Canada.
3
Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; and Department of Paediatrics and Physiology, University of Toronto, Toronto, Ontario, Canada.
4
Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; and Department of Paediatrics and Physiology, University of Toronto, Toronto, Ontario, Canada jaques.belik@sickkids.ca.

Abstract

The factors accounting for the pathological maintenance of a high pulmonary vascular (PV) resistance postnatally remain elusive, but neonatal stressors may play a role in this process. Cross-fostering in the immediate neonatal period is associated with adult-onset vascular and behavioral changes, likely triggered by early-in-life stressors. In hypothesizing that fostering newborn rats induces long-lasting PV changes, we evaluated them at 14 days of age during adulthood and compared the findings with animals raised by their biological mothers. Fostering resulted in reduced maternal-pup contact time when compared with control newborns. At 2 wk of age, fostered rats exhibited reduced pulmonary arterial endothelium-dependent relaxation secondary to downregulation of tissue endothelial nitric oxide synthase expression and tetrahydrobiopterin deficiency-induced uncoupling. These changes were associated with neonatal onset-increased ANG II receptor type 1 expression, PV remodeling, and right ventricular hypertrophy that persisted into adulthood. The pulmonary arteries of adult-fostered rats exhibited a higher contraction dose response to ANG II and thromboxane A2, the latter of which was abrogated by the oxidant scavenger Tempol. In conclusion, fostering-induced neonatal stress induces long-standing PV changes modulated via the renin-angiotensin system.

KEYWORDS:

neonatal stressors; pulmonary vasomotor tone; renin angiotensin system

PMID:
26342088
DOI:
10.1152/ajplung.00044.2015
[Indexed for MEDLINE]
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