Holgert H, Hökfelt T, Hertzberg T, Lagercrantz H
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7575-9. doi: 10.1073/pnas.92.16.7575.
The drive on respiration mediated by the peripheral arterial chemoreceptors was assessed by the hyperoxic test in 3-day-old rat pups. They accounted for 22.5 +/- 8.8% during control conditions, but only for 6.9 +/- 10.0% after nicotine exposure, an effect counteracted by blockade of peripheral dopamine type 2 receptors (DA2Rs). Furthermore, nicotine reduced dopamine (DA) content and increased the expression of tyrosine hydroxylase (TH) in the carotid bodies, further suggesting that DA mediates the acute effect of nicotine on arterial chemoreceptor function. During postnatal development TH and DA2R mRNA levels in the carotid bodies decreased. Thus, nicotine from smoking may also interfere with the postnatal resetting of the oxygen sensitivity of the peripheral arterial chemoreceptors by increasing carotid body TH mRNA, as well as DA release in this period. Collectively these effects of nicotine on the peripheral arterial chemoreceptors may increase the vulnerability to hypoxic episodes and attenuate the protective chemoreflex response. These mechanisms may underlie the well-known relation between maternal smoking and sudden infant death syndrome.
通过对3日龄幼鼠进行高氧试验,评估外周动脉化学感受器介导的呼吸驱动力。在对照条件下,外周动脉化学感受器介导的呼吸驱动力占22.5±8.8%,但在尼古丁暴露后仅占6.9±10.0%,外周多巴胺2型受体(DA2Rs)的阻断可抵消这一效应。此外,尼古丁降低了颈动脉体中的多巴胺(DA)含量,并增加了酪氨酸羟化酶(TH)的表达,进一步表明DA介导了尼古丁对动脉化学感受器功能的急性影响。在出生后发育过程中,颈动脉体中TH和DA2R mRNA水平下降。因此,吸烟产生的尼古丁也可能通过增加此时期颈动脉体TH mRNA以及DA释放,干扰外周动脉化学感受器对氧敏感性的出生后重置。尼古丁对外周动脉化学感受器的这些总体影响可能会增加对缺氧发作的易感性,并减弱保护性化学反射反应。这些机制可能是母亲吸烟与婴儿猝死综合征之间众所周知的关系的基础。