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

Yulia Shifrin1, Sina Sadeghi1, Jingyi Pan1

  • 1Physiology and Experimental Medicine Program, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; and.

Insights

Neonatal stress from fostering can cause lasting pulmonary vascular changes in rats. This includes reduced blood vessel relaxation and remodeling, influenced by the renin-angiotensin system.

Area of Science:

  • Physiology
  • Neonatology
  • Vascular Biology

Background:

  • Pulmonary vascular resistance can remain high postnatally due to unknown factors.
  • Neonatal stressors are implicated in long-term vascular and behavioral changes.
  • Cross-fostering is a model to study the impact of early-life stress.

Purpose of the Study:

  • To investigate if fostering newborn rats leads to persistent pulmonary vascular changes into adulthood.
  • To compare pulmonary vascular function and structure in fostered rats versus those raised by biological mothers.

Main Methods:

  • Rats were cross-fostered or raised by biological mothers.
  • Pulmonary vascular function was assessed at 14 days of age (adulthood).
  • Evaluations included endothelium-dependent relaxation, gene expression (e.g., nitric oxide synthase, ANG II receptor type 1), and vascular remodeling.

Main Results:

  • Fostered rats had reduced maternal-pup contact and impaired pulmonary arterial relaxation.
  • Downregulation of endothelial nitric oxide synthase and tetrahydrobiopterin deficiency were observed.
  • Increased ANG II receptor type 1 expression, pulmonary vascular remodeling, and right ventricular hypertrophy persisted into adulthood.
  • Adult fostered rats showed heightened pulmonary artery contraction to ANG II and thromboxane A2.

Conclusions:

  • Fostering-induced neonatal stress results in enduring pulmonary vascular alterations.
  • These changes are mediated through the renin-angiotensin system.
  • Early-life stress impacts long-term cardiovascular health.

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