Journal article
Maternal-pup interaction disturbances induce long-lasting changes in the newborn rat pulmonary vasculature
American journal of physiology. Lung cellular and molecular physiology, Vol.309(10), pp.L1186-L1198
11/15/2015
DOI: 10.1152/ajplung.00044.2015
PMID: 26342088
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.
Details
- Title: Subtitle
- Maternal-pup interaction disturbances induce long-lasting changes in the newborn rat pulmonary vasculature
- Creators
- Yulia Shifrin - Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; andSina Sadeghi - Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; andJingyi Pan - Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; andAmish Jain - Department of Paediatrics and Physiology, University of Toronto, Toronto, Ontario, CanadaAndres F Fajardo - Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; andPatrick J McNamara - 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, CanadaJaques Belik - 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
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.309(10), pp.L1186-L1198
- DOI
- 10.1152/ajplung.00044.2015
- PMID
- 26342088
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Grant note
- MOP 133664 / Canadian Institutes of Health Research
- Language
- English
- Date published
- 11/15/2015
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology; Internal Medicine
- Record Identifier
- 9984093493202771
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