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.

中文翻译：

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对乙酰氨基酚增加新生大鼠的肺和全身血管舒缩张力

背景 由于各种原因，对乙酰氨基酚被广泛用于新生儿和幼儿。在成人中，对乙酰氨基酚的治疗用途会引起全身动脉压变化，而高剂量暴露会促进组织毒性。对乙酰氨基酚在任何年龄对肺血管的影响尚不清楚。假设在生命早期，它通过氧化应激促进血管舒缩性变化，我们测试了体外对乙酰氨基酚对新生和成年大鼠肺内和颈动脉的影响。方法 我们测量了等长动脉中对乙酰氨基酚的剂量反应，并在药理学上评估了解释其血管舒缩效应的因素。结果 对乙酰氨基酚引起浓度和年龄依赖性血管舒缩张力变化。而在新生儿中观察到血管舒缩张力逐渐增加，成人动脉主要表现为血管舒张。用 l-NAME 抑制内源性一氧化氮的产生和使用过氧亚硝酸盐分解催化剂 FeTPPS（Fe（III）5,10,15,20-四（4-磺基苯基）卟啉氯化物）主要消除了新生儿药物诱导的增加肺血管舒缩 结论 在新生大鼠中，对乙酰氨基酚通过产生过氧亚硝酸盐增加肺血管舒缩。鉴于其治疗用途，需要进一步的临床研究来评估对乙酰氨基酚对新生儿肺和全身血管阻力的影响。20-四（4-磺基苯基）卟啉氯化物）主要消除了药物诱导的新生肺血管舒缩张力增加结论在新生大鼠中，对乙酰氨基酚通过产生过氧亚硝酸盐增加肺血管舒缩张力。鉴于其治疗用途，需要进一步的临床研究来评估对乙酰氨基酚对新生儿肺和全身血管阻力的影响。20-四（4-磺基苯基）卟啉氯化物）主要消除了药物诱导的新生肺血管舒缩张力增加结论在新生大鼠中，对乙酰氨基酚通过产生过氧亚硝酸盐增加肺血管舒缩张力。鉴于其治疗用途，需要进一步的临床研究来评估对乙酰氨基酚对新生儿肺和全身血管阻力的影响。