Control of the pulmonary circulation in the fetus and during the transitional period to air breathing
Control of the pulmonary circulation in the fetus and during the transitional period to air breathing
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DOI：
10.1016/s0301-2115(98)00321-2
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发表时间：
1999-06-01
影响因子：
2.6
通讯作者：
Heymann, MA
中科院分区：
文献类型：
--
作者：
Heymann, MA
在胎儿生活和过渡到子宫外的空气呼吸，肺血管张力是由一个复杂的，相互作用的机制组调节。花生四烯酸代谢物在这一调控中起重要作用。虽然前列腺素可能不是调节胎儿静息肺循环的核心，但PGI(2)可以调节张力，从而维持肺血管阻力相对恒定。PGI(2)也可能作为与空气呼吸开始时发生的主要变化有关的组成部分之一发挥重要作用。白三烯，也是花生四烯酸和强效平滑肌收缩剂的代谢产物，可能在维持正常的高胎儿肺血管阻力中发挥积极作用，因为白三烯受体阻断或合成抑制使肺血流量增加约8倍；胎儿气管液中白三烯的存在进一步支持了这一点。除了PGI(2)外，血管内皮细胞还产生其他血管活性因子。其中包括有效的血管扩张剂，如内皮源性松弛因子（EDRF）。EDRF，已知是一氧化氮（NO），通常称为内皮源性一氧化氮（EDNO），是由内皮细胞对各种刺激反应产生的，通常涉及特定受体和内皮NO合成酶（eNOS）的激活；随后的平滑肌松弛是由NO/ guanyyl环化酶/ cgmp介导的机制产生的。NO显然参与了胎儿肺循环血管张力的调节，尽管它在出生后向空气呼吸的过渡中起着更重要的作用。缓激肽刺激过度的胎羊肺动脉释放NO。在胎儿羔羊中，亚甲基蓝减弱缓动素的血管舒张作用，NO-硝基- l -精氨酸（NO合成抑制剂）降低静息张力，表明NO/ cgmp依赖机制持续调节或抵消静息胎儿肺循环张力的增加。抑制NO合成可阻断子宫内胎儿肺氧合的肺血管舒张。剪切应力诱导的NO生成以及氧化与NO生成的关系进一步支持了NO在这一转变中的重要作用。尽管内皮素-1 （ET-1）在肺血管抵抗中具有强大的血管活性和个体发生差异，但其确切的生理作用尚未明确。肾上腺髓质素和降钙素基因相关肽（CGRP）是另外两种血管活性物质，在胎儿肺循环中具有深远而持久的血管舒张作用。它们的生理作用尚未确定。1999爱思唯尔科学爱尔兰有限公司版权所有。
During fetal life and the transition to extra-uterine air breathing, pulmonary vascular tone is regulated by a complex, interactive group of mechanisms. Arachidonic acid metabolites play an important role in this regulation. Although prostaglandins may not be central to regulation of the resting fetal pulmonary circulation, PGI(2) acts to modulate tone and thereby maintain pulmonary vascular resistance relatively constant. PGI(2) also may play an important role as one of the components involved in the major changes that occur with the onset of air breathing. Leukotrienes, also metabolites of arachidonic acid and potent smooth muscle constrictors, may play an active role in maintaining the normally high fetal pulmonary vascular resistance, because leukotriene receptor blockade or synthesis inhibition increases pulmonary blood flow about eight-fold; the presence of leukotrienes in fetal tracheal fluid further supports this. In addition to PGI(2), vascular endothelial cells produce other vasoactive factors. These include potent vasodilators, such as endothelium-derived relaxing factor (EDRF). EDRF, known to be nitric oxide (NO) and often called endothelium-derived nitric oxide (EDNO), is produced by endothelial cells in response to varied stimuli, generally involving specific receptors and the activation of endothelial NO synthetase (eNOS); subsequent smooth muscle relaxation is produced by a NO/guanylyl cyclase/cGMP-mediated mechanism. NO clearly is involved in regulation of vascular tone in the fetal pulmonary circulation, although it plays a far more important role in the postnatal transition to air breathing. Superfused fetal sheep pulmonary arteries release NO when stimulated with bradykinin. In fetal lambs the vasodilating effects of bradykinin are attenuated by methylene blue and resting tone falls with NO-nitro-L-arginine, an inhibitor of NO synthesis, suggesting that a NO/cGMP-dependent mechanism continuously modulates or offsets the increased tone of the resting fetal pulmonary circulation. Inhibition of NO synthesis blocks the pulmonary vasodilation with oxygenation of fetal lungs in utero. Shear stress-induced NO production as well as the relationship of oxygenation to NO production further support the important function of NO in the transition. Although endothelin-1 (ET-1) has potent vasoactivity as well as ontogenetic differences in effect on pulmonary vascular resistance, its exact physiological role has not been defined. Adrenomedullin and calcitonin gene-related peptide (CGRP), two additional vasoactive substances, have profound, and prolonged, vasodilating effects in the fetal pulmonary circulation. Their physiological roles have not yet been established. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.