CHARACTERIZATION OF VASCULAR TONE ON LUNG FLUID BALANCE

这项研究提案的主要目标是测试 肺血管张力升高和肺损伤改变的假说 组胺能、胆碱能和肾上腺素能介导的肺 血管反应，使肺毛细血管压力和 微血管通透性受到影响，从而扰乱肺液 平衡。具体地说，这项提议将：1)体现不同的特点 节段性血管张力升高的模型 血管阻力顺应性和微血管的分布 渗透性。要测试的升高血管张力的模型包括 U46619(血栓素类似物)、内皮素-I(缩血管肽)、 去甲肾上腺素和血管紧张素11.2)比较了 组胺、胆碱和肾上腺素能受体的激活 系统处于正常血管张力，并使用 上述模型和应用佛波酯的肺损伤 醋酸(PMA)滴注、油酸滴注、盐酸气道滴注。 3)比较主动增加血管张力和被动增加血管张力的效果 当刺激上述受体系统时，血管扩张； 以及4)评估当组胺能， 胆碱能和肾上腺素能受体系统在肺中被激活 血管张力正常，血管张力升高，还有损伤。细分市场 肺血管阻力和顺应性的分布 通过使用单独的动脉、静脉和双血管来确定 遮挡技术。肺微血管通透性将 通过测量毛细管过滤系数进行评估， 等渗毛细管压力和渗透反射 系数。除了生理测量，表征 组胺能、胆碱能和肾上腺素能受体系统 通过动力学速率常数测量进行药理学评估 通过分析血管活性介质的存在来进行生化分析。这个 被动扩张血管对这些受体介导效应的影响 将通过不同静水压力的灌流进行评估。 最后，受体刺激下的肺血流模式将是 通过观察锌镉硫化物的分布进行评价 (黄色荧光血管标记物)在对照中，血管色调，和 肺部受伤。

The major objective of this research proposal is to test the hypothesis that elevated pulmonary vascular tone and lung injury alter the histaminergic, cholinergic, and adrenergic-mediated pulmonary vascular responses such that both pulmonary capillary pressure and microvascular permeability are affected, thereby disrupting lung fluid balance. Specifically, this proposal will: 1) characterize different models of elevated vascular tone with respect to the segmental distribution of vascular resistance-compliance, and microvascular permeability. The models of elevating vascular tone to be tested include U46619 (thromboxane analog), endothelin-I (vasoconstrictor peptide), norepinephrine, and angiotensin 11. 2) compare the responses to the activation of the histaminergic, cholinergic, and adrenergic receptor systems at normal vascular tone, and elevated vascular tone using the models outlined above, and following lung injury using phorbol myristate acetate (PMA) infusion, oleic acid infusion and HCL airway instillation. 3) compare the effect of active increases in vascular tone to passive vessel distention when the receptor systems stated above are stimulated; and 4) evaluate blood flow patterns that occur when the histaminergic, cholinergic, and adrenergic receptor systems are activated in lungs with normal vascular tone, elevated vascular tone, and injury. The segmental distribution of pulmonary vascular resistance and compliance will be determined by use of separate arterial, venous, and double vascular occlusion techniques. Pulmonary microvascular permeability will be evaluated by measurement of the capillary filtration coefficient, isogravimetric capillary pressure, and the osmotic reflection coefficient. In addition to physiological measurements, characterization of the histaminergic, cholinergic, and adrenergic receptor systems will be evaluated pharmacologically by kinetic rate-constant measurements and biochemically by assaying for the presence of vasoactive mediators. The effect of passive vessel distention on these receptor-mediated effects will be assessed by perfusion with different hydrostatic pressures. Finally, pulmonary blood flow patterns upon receptor stimulation will be evaluated by observing the distribution of zinc cadmium sulfide compound (a yellow fluorescing vascular marker) in control, vascular toned, and injured lungs.