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

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.

Programming of Vascular Dysfunction by Maternal Stress: Immune System Implications

“…Yet, brief periods of daily maternal separation lead to impaired resistance artery due augmented vascular contractility-response and higher blood pressure in adult rats ( Reho and Fisher, 2015 ). Even the pulmonary vasculature may be affected by stressor conditions, including cross-fostering in early natal period, through renin–angiotensin system modulation ( Shifrin et al, 2015 ).…”

Update on novel targets and potential treatment avenues in pulmonary hypertension

“…During CH, levels of Ser1177 phosphorylated eNOS are markedly reduced (138) in adult animals. In newborns, oxidative stress also caused persistent downregulation of the NO pathway that resulted in enhanced PA contractility and muscularity and RV hypertrophy that persisted into adulthood (218). Along these lines, lung NOS levels were reduced in an experimental model of congenital diaphragmatic hernia (CDH) in fetal rats (153).…”