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动脉导管氧感应-两个概念的统一认识。

Oxygen sensing in the ductus arteriosus-A unifying vision for two concepts.

机构信息

Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.

出版信息

Br J Pharmacol. 2022 Jul;179(13):3325-3329. doi: 10.1111/bph.15828. Epub 2022 Mar 18.

Abstract

Closure of the ductus arteriosus at birth is known to be related to the physiological rise in blood oxygen tension. Two main schemes have been proposed to explain the peculiar contraction of the ductus to oxygen, and their function is based on distinct sensor-effector complexes. Specifically, these schemes comprise a cytochrome P450 monooxygenase-endothelin complex or, alternatively, a mitochondrial redox mechanism-voltage gated potassium channel complex. However, it is not clear how these systems may relate to the closure process. Here, it is proposed that they operate jointly within a single functional entity, with their combined activation being required for a full-fledged contraction of the vessel to oxygen. This arrangement is thought to ensure a smooth transition from the powerful relaxant mechanism that is evident through the early postnatal period. Validation of this concept would not only settle a central question in the operation of the ductus but may also afford a broader perspective in any future translational research.

摘要

动脉导管在出生时的关闭被认为与血液氧张力的生理上升有关。有两种主要的方案被提出来解释导管对氧气的特殊收缩,它们的功能基于不同的传感器-效应器复合物。具体来说,这些方案包括细胞色素 P450 单加氧酶-内皮素复合物,或者替代地,线粒体氧化还原机制-电压门控钾通道复合物。然而,这些系统如何与关闭过程相关尚不清楚。在这里,我们提出它们在单个功能实体中共同运作,它们的联合激活是血管对氧气充分收缩所必需的。这种安排被认为可以确保从强大的松弛机制平稳过渡,这种机制在出生后的早期阶段非常明显。验证这一概念不仅可以解决动脉导管功能中的一个核心问题,而且还可以为未来的任何转化研究提供更广泛的视角。

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