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OXYGEN TENSION AND ENDOTHELIUM-DEPENDENT VASODILATION

氧张力和内皮依赖性血管舒张

基本信息

批准号：
3471728
负责人：
Roger A Johns
金额：
$ 11.56万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-03-01 至 1993-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3471728
关键词：
adult respiratory distress syndrome cell bank /registry cyclic GMP laboratory rabbit muscle relaxing factor oxygen tension pulmonary circulation pulmonary hypertension vascular endothelium vascular smooth muscle vasodilation

项目摘要

The role of the endothelium has taken on increasing significance in vascular pharmacology and physiology in the past several years with the discovery that numerous endogenous and exogenous vasodilators exert their action on vascular smooth muscle by releasing from the endothelium a substance termed endothelium- dependent relaxing factor (EDRF). The production of EDRF is calcium dependent; it has a short biologic half-life; and its relaxing action on vascular smooth muscle correlates with an increase in muscle cyclic GMP concentration. Several studies have implicated the importance of oxygen tension in the stability of the relaxation responses induced by EDRF. The proposed research plan will investigate the inhibition of endothelium dependent relaxation by hypoxia. The oxygen sensitivity of these responses could be due to an effect on factor production, to the stability of EDRF once produced, to the reactivity of the vascular smooth muscle where it acts, or to some combination of these events. An experimental system will be used which allows transfer of EDRF from cultured pulmonary artery endothelial cells to one of three bioassays: relaxation of a de-endothelialized vascular ring, increase in cyclic GMP levels in cultured-vascular smooth muscle, or activation of guanylate cyclase. Separate manipulation of the oxygen tensions of the endothelial cells, of EDRF in solution, and of the bioassay preparations will allow us to investigate the sites and mechanisms of oxygen interactions with EDRF. The effects of varying oxygen tensions on the increase in endothelial cell cytoplasmic calcium concentration which normally accompanies EDRF release also will be determined. In addition to providing further insight into the nature of EDRF, these studies will increase our understanding of the potential role of EDRF in the normal and diseased pulmonary circulation including regulation of basal tone, hypoxic pulmonary vasoconstriction, pulmonary hypertension, and adult respiratory distress syndrome.

内皮细胞的作用越来越重要血管药理学和生理学的研究进展随着许多内源性和外源性的发现，血管扩张剂通过以下方式对血管平滑肌发挥作用：从内皮释放一种称为内皮的物质，依赖性舒张因子（EDRF）。 EDRF的生产是钙依赖性;它具有短的生物半衰期;其对血管平滑肌的舒张作用与增加肌肉环GMP浓度。几项研究暗示了氧张力在稳定性中的重要性 EDRF诱导的弛豫反应。拟议的研究计划将研究抑制缺氧引起的内皮依赖性舒张。氧这些反应的敏感性可能是由于对因素的影响，生产，EDRF一旦生产的稳定性，血管平滑肌作用处的反应性，或这些事件的组合。一个实验系统将可以将EDRF从培养的肺细胞中转移动脉内皮细胞的三个生物测定之一：松弛的去内皮化的血管环，培养的血管平滑肌，或激活鸟苷酸环化酶单独操纵的氧张力的内皮细胞，EDRF溶液，和生物测定准备工作将使我们能够调查的网站和机制氧与EDRF的相互作用。不同氧气的影响张力对内皮细胞胞浆钙离子浓度的影响通常伴随EDRF释放的浓度也将被确定。除了提供对EDRF性质的进一步了解之外，这些研究将增加我们对正常和病变肺循环中EDRF的浓度包括调节基础张力、低氧性肺动脉高压血管收缩、肺动脉高压和成人呼吸道疾病痛苦综合症