OXYGEN MODULATION OF FETAL VASCULAR ENDOTHELIUM

胎儿血管内皮的氧调节

• 批准号: 2226081
• 负责人: LOREN P THOMPSON
• 金额: $ 9.4万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226081
• 关键词: carotid artery; electrodes; electromyography; embryo /fetus; gestational age; guinea pigs; mature animal; mesenteric artery; newborn animals; nitric oxide; oxygen tension; pulmonary artery; radioimmunoassay; statistics /biometry; vascular endothelium; vascular resistance; vasoconstriction; vasodilation; vasodilators; vasomotion

Obstetric complications resulting in reduced uteroplacental perfusion greatly increase fetal mortality. Under these circumstances, fetal vascular adjustments are required to maintain adequate perfusion of organs critical for the normal growth and development of the fetus. The fetus responds to hypoxemia by redistributing cardiac output to organs such as the heart, brain, and adrenal gland The vascular mechanisms underlying this redistribution are poorly understood. In the adult circulation, the endothelium modulates vascular tone by release of vasoactive substances and is influenced by changes in oxygen tension. We hypothesize that fetal endothelium modulates vascular tone by releasing vasoactive autacoids in response to changes in oxygen tension. We further hypothesize that, in vivo, the fetal endothelium is an important oxygen sensing site and influences vascular reactivity to circulating hormones via oxygen-sensitive mechanisms. The effect of changes in oxygen tension on endothelium-dependent relaxation and agonist-induced contraction will be measured in isolated carotid and pulmonary arteries from guinea pig fetuses from 0.5 to near term gestation. Further, the vascular responses of isolated perfused mesenteric preparations will be measured to study reactivity of resistance-sized arteries. The response of the endothelium to changes in oxygen will be investigated in arteries from newborn and adult guinea pigs to characterize the adaptive changes in the endothelium after birth. SPECIFIC AIMS: 1) To determine the effect of gestational age on endothelium-dependent mechanisms in fetal arteries. 2) To determine the effect of oxygen on endothelium-dependent modulation of contraction and relaxation of isolated fetal arteries. 3) To determine the effect of maturation on oxygen sensitivity of the endothelium between fetal, newborn, and adult arteries.

产科并发症导致子宫胎盘灌注减少 大大增加胎儿死亡率。 在这种情况下，胎儿 需要调整血管以维持足够的灌注 对胎儿正常生长发育至关重要的器官。 这 胎儿通过将心输出量重新分配到器官来应对低氧血症 例如心脏、大脑和肾上腺 血管机制 人们对这种重新分配的背后知之甚少。 在成人中 循环中，内皮细胞通过释放 血管活性物质，并受到氧张力变化的影响。 我们假设胎儿​​内皮通过以下方式调节血管张力 响应氧张力的变化释放血管活性自体物质。 我们进一步假设，在体内，胎儿内皮细胞是 重要的氧感应位点并影响血管反应性 通过氧敏感机制循环激素。 的效果 氧张力的变化对内皮依赖性舒张的影响 激动剂诱导的收缩将在分离的颈动脉中测量 豚鼠胎儿的肺动脉从0.5到近期 妊娠。 此外，分离灌注的血管反应 将测量肠系膜制剂以研究其反应性 阻力大小的动脉。 内皮细胞对变化的反应 将在新生儿和成年几内亚的动脉中研究氧气 猪出生后表征内皮的适应性变化。 具体目标： 1) 确定胎龄对内皮依赖性的影响 胎儿动脉的机制。 2) 确定氧对内皮依赖性调节的影响 胎儿离体动脉的收缩和舒张。 3) 确定成熟对氧敏感性的影响 胎儿、新生儿和成人动脉之间的内皮。