Background Birth asphyxia is associated with neonatal acidosis in arterial blood following delivery of the baby. Acidosis during asphyxia is accompanied by the drop of blood pressure level that might be associated with the decrease of peripheral vascular resistance. However, the mechanisms of arterial relaxation in response to acidosis in the early postnatal period are scarce. We hypothesized that in early postnatal period the substantial contribution of Rho-kinase to the regulation of arterial tone is decreased under conditions of acidosis. Methods We modeled extracellular metabolic acidosis (pH = 6.8) and studied isolated saphenous arteries of 11–14-day-old rats by wire myography, Ca2+-fluorimetry and Western blotting. Results Acidosis reduced contraction and [Ca2+]i elevation in response α1-adrenoceptor agonist methoxamine in arteries of 11–14-day-old rats. Rho-kinase inhibitor Y27632 weakened contractile responses of arteries both at pH = 7.4 and pH = 6.8. The influence of Y27632 was stronger at pH = 7.4 compared to pH = 6.8. MYPT1 phosphorylation at Thr855 (marker of Rho-kinase activity) in the presence of methoxamine was significantly larger at pH = 7.4 compared to pH = 6.8. At both pH Y27632 reduced MYPT1 phosphorylation level to equal values, confirming the dependence of such phosphorylation on Rho-kinase activity. Conclusion Our data demonstrate that acidosis suppresses Rho-kinase procontractile impact in arteries in early postnatal period. Impact <UnorderedList Mark="Bullet"> <ItemContent> Birth asphyxia is associated with acidosis in neonates. Acidosis during asphyxia is accompanied by the drop of blood pressure level that might be associated with the decrease of peripheral vascular resistance. </ItemContent> <ItemContent> Acidosis has a complex effect on the vascular tone regulation in the early postnatal period, affecting procontractile and anticontractile mechanisms in different directions. </ItemContent> <ItemContent> Acidosis suppresses Rho-kinase procontractile impact in arteries in early postnatal period. </ItemContent> </UnorderedList>

Decrease of Rho-kinase functional activity as potential complication of birth asphyxia in newborn vasculature

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发表日期：

2025年11月25日

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Anastasia A. Shvetsova,
Anna A. Borzykh,
Dina K. Gaynullina

摘要

Background

Birth asphyxia is associated with neonatal acidosis in arterial blood following delivery of the baby. Acidosis during asphyxia is accompanied by the drop of blood pressure level that might be associated with the decrease of peripheral vascular resistance. However, the mechanisms of arterial relaxation in response to acidosis in the early postnatal period are scarce. We hypothesized that in early postnatal period the substantial contribution of Rho-kinase to the regulation of arterial tone is decreased under conditions of acidosis.

Methods

We modeled extracellular metabolic acidosis (pH = 6.8) and studied isolated saphenous arteries of 11–14-day-old rats by wire myography, Ca²⁺-fluorimetry and Western blotting.

Results

Acidosis reduced contraction and [Ca²⁺]_i elevation in response α₁-adrenoceptor agonist methoxamine in arteries of 11–14-day-old rats. Rho-kinase inhibitor Y27632 weakened contractile responses of arteries both at pH = 7.4 and pH = 6.8. The influence of Y27632 was stronger at pH = 7.4 compared to pH = 6.8. MYPT1 phosphorylation at Thr855 (marker of Rho-kinase activity) in the presence of methoxamine was significantly larger at pH = 7.4 compared to pH = 6.8. At both pH Y27632 reduced MYPT1 phosphorylation level to equal values, confirming the dependence of such phosphorylation on Rho-kinase activity.

Conclusion

Our data demonstrate that acidosis suppresses Rho-kinase procontractile impact in arteries in early postnatal period.

Impact

Birth asphyxia is associated with acidosis in neonates. Acidosis during asphyxia is accompanied by the drop of blood pressure level that might be associated with the decrease of peripheral vascular resistance.

Acidosis has a complex effect on the vascular tone regulation in the early postnatal period, affecting procontractile and anticontractile mechanisms in different directions.

Acidosis suppresses Rho-kinase procontractile impact in arteries in early postnatal period.