OXYGEN MODULATION OF FETAL VASCULAR ENDOTHELIUM

产科并发症导致子宫胎盘灌注量减少 极大地增加了胎儿死亡率。在这种情况下，胎儿 需要进行血管调节以维持足够的血流灌注 对胎儿的正常生长和发育至关重要的器官。这个 胎儿对低氧血症的反应是将心输出量重新分配到器官 如心脏、大脑和肾上腺的血管机制 这种再分配背后的原因人们知之甚少。在成人中 循环，内皮通过释放血管紧张素来调节血管张力 血管活性物质，受氧分压变化的影响。 我们假设胎儿内皮通过以下途径调节血管张力 释放血管活性类耳石以回应氧分压的变化。 我们进一步假设，在活体内，胎儿内皮是一种 重要的氧敏感部位，并影响血管的反应性 通过氧敏感机制使荷尔蒙循环。的影响 氧分压变化对内皮依赖性松弛和血管内皮功能的影响 激动剂诱导的收缩将在分离的颈动脉和 豚鼠胚胎0.5~近足月的肺动脉 怀孕了。此外，离体血灌流的血管反应 肠系膜制剂将被测量以研究其反应性 阻力大小的动脉。血管内皮细胞对血管内皮细胞变化的反应 将对新生儿和成年几内亚的动脉中的氧气进行调查。 以表征猪出生后内皮细胞的适应性变化。 具体目标： 1)探讨胎龄对血管内皮依赖性的影响 胎儿动脉的机制。 2)确定氧对内皮依赖性调节的影响 离体胎动脉的收缩和松弛。 3)测定成熟度对乳酸菌氧敏感性的影响。 胎儿动脉、新生儿动脉和成人动脉之间的内皮。

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.