Liran Tamir Hostovsky1, Jingyi Pan2, Patrick J McNamara1, Jaques Belik3,4. 1. Department of Paediatrics, University of Toronto, Toronto, ON, M5G 1X8, Canada. 2. Translational Medicine Program, Department of Paediatrics, The Hospital for Sick Children Research Institute, Toronto, ON, M5G 1X8, Canada. 3. Translational Medicine Program, Department of Paediatrics, The Hospital for Sick Children Research Institute, Toronto, ON, M5G 1X8, Canada. jaques.belik@utoronto.ca. 4. Department of Paediatrics Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada. jaques.belik@utoronto.ca.
Abstract
BACKGROUND: Acetaminophen is widely prescribed to both neonates and young children for a variety of reasons. In adults, therapeutic usage of acetaminophen induces systemic arterial pressure changes and exposure to high doses promotes tissue toxicity. The pulmonary vascular effects of acetaminophen at any age are unknown. Hypothesizing that, early in life, it promotes vasomotor tone changes via oxidative stress, we tested the in vitro acetaminophen effects on intrapulmonary and carotid arteries from newborn and adult rats. METHOD: We measured the acetaminophen dose-response in isometrically mounted arteries and pharmacologically evaluated the factors accounting for its vasomotor effects. RESULTS: Acetaminophen induced concentration- and age-dependent vasomotor tone changes. Whereas a progressive increase in vasomotor tone was observed in the newborn, the adult arteries showed mostly vasorelaxation. Inhibition of endogenous nitric oxide generation with L-NAME and the use of the peroxynitrite decomposition catalyst FeTPPS (Fe(III)5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato chloride) mostly abolished the drug-induced increase in newborn pulmonary vasomotor tone CONCLUSIONS: In newborn rats, acetaminophen increases pulmonary vasomotor tone via peroxynitrite generation. Given its therapeutic usage, further clinical studies are warranted to assess the acetaminophen effects on the newborn pulmonary and systemic vascular resistance.
BACKGROUND:Acetaminophen is widely prescribed to both neonates and young children for a variety of reasons. In adults, therapeutic usage of acetaminophen induces systemic arterial pressure changes and exposure to high doses promotes tissue toxicity. The pulmonary vascular effects of acetaminophen at any age are unknown. Hypothesizing that, early in life, it promotes vasomotor tone changes via oxidative stress, we tested the in vitro acetaminophen effects on intrapulmonary and carotid arteries from newborn and adult rats. METHOD: We measured the acetaminophen dose-response in isometrically mounted arteries and pharmacologically evaluated the factors accounting for its vasomotor effects. RESULTS:Acetaminophen induced concentration- and age-dependent vasomotor tone changes. Whereas a progressive increase in vasomotor tone was observed in the newborn, the adult arteries showed mostly vasorelaxation. Inhibition of endogenous nitric oxide generation with L-NAME and the use of the peroxynitrite decomposition catalyst FeTPPS (Fe(III)5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato chloride) mostly abolished the drug-induced increase in newborn pulmonary vasomotor tone CONCLUSIONS: In newborn rats, acetaminophenincreases pulmonary vasomotor tone via peroxynitrite generation. Given its therapeutic usage, further clinical studies are warranted to assess the acetaminophen effects on the newborn pulmonary and systemic vascular resistance.
Authors: Kristin L Santoro; William Yakah; Pratibha Singh; David Ramiro-Cortijo; Esli Medina-Morales; Steven D Freedman; Camilia R Martin Journal: J Pediatr Date: 2022-01-31 Impact factor: 6.314