Functional Heterogeneity of Pulmonary Arteries and Veins

在肺循环中，动脉和静脉表现出结构性和功能性。 在组织、细胞和分子水平上的异质性。我们已经报道过，在围产期 (胎儿期和新生儿期)，肺动、静脉都非常发达。 血管活性和静脉对总肺血管阻力有显著贡献。在子宫里， 整个血管树都暴露在胎儿血液的低氧分压下。然而，紧接着 出生时，静脉暴露在含氧血液中，而动脉继续暴露在 脱氧血液。因此，我们假设观察到的功能行为的异质性 出生后的肺动静脉可以部分地用差异效应来解释。 由肺动静脉中的氧气暴露所致。我们的具体目标是基于我们的 初步数据表明，暴露在氧气中会增加cGMP依赖的蛋白激酶 (PKG)介导的肺静脉血管扩张，而不是动脉。基于这个观察，我们的 主要假设是肺组织中产生的活性物质的数量和类型(S) 动脉和静脉SMC对氧分压变化的反应不同，导致不同 动脉和静脉中的细胞信号事件和反应。我们相信我们背后的机制 氧对cGMP介导的肺松弛作用的异质性观察 动脉和静脉可能为肺的异质性反应提供了一个共同的解释 动脉和静脉。在这项建议中，我们将确定活性氧物种在 肺动、静脉的异质性行为。我们将确定类型(S)、金额和地点 (S)肺动脉和静脉平滑肌产生活性氧和氮的研究 并测定了这些活性物种对PKG蛋白含量、活性和PKG依赖性的影响 肺动、静脉的松弛反应。我们还将确定活性氧的作用 不同物种对肺动脉和静脉血管中PKG基因表达的影响。

In the pulmonary circulation, arteries and veins demonstrate structural and functional heterogeneity, at the tissue, cellular and molecular level. We have reported that in the perinatal period (during fetal life and in the immediate newborn period), both pulmonary arteries and veins are very vasoactive and that veins contribute significantly to total pulmonary vascular resistance. In utero, the entire vascular tree is exposed to the low oxygen tension of fetal blood. However, immediately after birth, veins are exposed to oxygenated blood whereas the arteries continue to be exposed to de-oxygenated blood. We therefore hypothesize that the observed heterogeneity in functional behavior of pulmonary arteries and veins in the postnatal period may in part be explained by differential effects induced by oxygen exposure in pulmonary arteries and veins. Our specific aims are based on our preliminary data which demonstrate that exposure to oxygen augments cGMP-dependent protein kinase (PKG)-mediated vasodilation in pulmonary veins but NOT in arteries. Based on this observation, our main hypothesis is that the amount and type(s) of reactive species that are generated in pulmonary arterial versus venous SMC in response to changes in oxygen tension are different, resulting in different cell signaling events and responses in arteries and veins. We believe that the mechanisms behind our observation that there is heterogeneity in oxygen effects on cGMP-mediated relaxation in pulmonary arteries and veins might provide a common explanation for heterogeneous responses in pulmonary arteries and veins. In this proposal, we will determine the role of reactive oxygen species in the heterogeneous behavior of pulmonary arteries and veins. We will determine the type (s), amount and site (s) of production of reactive oxygen and nitrogen species in pulmonary artery and vein smooth muscle and determine the effect of these reactive species on PKG protein amount, activity and PKG-dependent relaxation responses in pulmonary arteries and veins. We will also determine the role of reactive oxygen species on PKG gene expression in pulmonary artery and vein smooth muscle.