PROSTAGLANDIN METABOLISM IN HUMAN BLOOD VESSELS

人体血管中的前列腺素代谢

• 批准号: 3340568
• 负责人: DENNIS B MCNAMARA
• 金额: $ 7.97万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3340568
• 关键词: arachidonate; blood vessels; eicosanoid metabolism; hormone regulation /control mechanism; human tissue; hypertension; ionophores; lipoxygenase; microsomes; muscle cells; muscle proteins; muscle tone; oxygenases; radiotracer; vascular smooth muscle; vasoactive agent

The long-term objective of the proposed research is to improve our understanding of the mechanisms involved in the control of vascular tone. Fundamental knowledge of the cellular mechanisms which regulate vascular smooth muscle tone is needed for the development o new forms of treatment and drugs directed at vascular disease such as hypertension. The aims of this proposal are to explore the metabolism of arachidonic acid, the precursor of a variety of vasoactive substances, using human and bovine intrapulmonary artery and vein, human and canine saphenous vein and human aortic buttons from the ascending aorta. Radiolabelled arachidonic acid or prostaglandin endoperoxide 14C-PGH2 will be employed as substrates. The substrate will be incubated with rings or microsomes from the vascular segments. The effects of varying the concentrations of enzyme and substrate, time of incubation, pH and temperature will be determined. The effects of cofactors such as glutathione and various inhibitors such as indomethacin on the formation of product of arachidonic acid will be determined. Comparisons of the in vitro arachidonic acid and PGH2 metabolism of artery vs. vein, artery vs. artery and vein vs. vein in different vascular beds in different species will be made. Additionally, the responses of the intact canine saphenous vein to endogenous (ionophore-stimulated) and exogenous arachidonic acid will be determined and correlated with the canine saphenous vein in vitro studies. The unifying goal of this proposal is to improve our knowledge of the regulation of vascular smooth muscle.

拟议研究的长期目标是改善我们的 了解控制血管张力的机制。 调节血管的细胞机制的基本知识 开发o新形式的治疗需要平滑肌肉 和针对血管疾病的药物，例如高血压。 目的 该建议是探索花生四烯酸的代谢， 使用人和牛的多种血管活性物质的前体 肺内动脉和静脉，人类和犬的隐静脉和人类 升主动脉的主动脉按钮。 放射性标记的花生四烯酸或 前列腺素内氧化物14C-PGH2将被用作底物。 这 底物将与血管中的环或微粒孵育 细分市场。 改变酶和浓度的影响 将确定底物，孵育时间，pH和温度。 这 辅助因子（例如谷胱甘肽和各种抑制剂）的影响 吲哚美辛的吲哚美辛会是 决定。 比较体外的花生四烯酸和PGH2 动脉的代谢与静脉，动脉和静脉与静脉的代谢 将制作不同物种的不同血管床。 此外， 完整的犬隐静脉对内源性的反应 （离子团刺激）和外源性花生四烯酸将被确定 并在体外研究中与犬类隐静脉相关。 这 该提议的统一目标是提高我们对 调节血管平滑肌。