PERIPHERAL VASCULAR CONTROL MECHANISMS

外周血管控制机制

• 批准号: 3346593
• 负责人: BARRY M CHAPNICK
• 金额: $ 16.75万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346593
• 关键词: capillary bed; dogs; gastrointestinal circulation; hemodynamics; hypertension; kidney circulation; leukotrienes; lipoxygenase; peripheral blood vessel; vascular smooth muscle; vasoactive agent; vasomotion

Arachidonic acid serves as the common natural precursor of at least two families of biologically active compounds. Metabolism of arachidonate via the cyclooxygenase pathway gives rise to bisenoic prostaglandin, prostacyclin and thromboxane, whereas derivatives formed via the 5'-lipoxygenase pathway include hydroperoxy acids, hydroxy acids and leukotrienes (LT). It is well-established that vasoactivity of arachidonic acid is dependent on conversion to active metabolites. Although cyclooxygenase products have been extensively studied, the leukotriene family of compounds are of more recent discovery, and influences of these products on regional blood flow and vasomotor tone are not well-established. A long term goal of these studies is to enhance our knowledge of the relationships of ieukotrienes to control of regional hemodynamics. We have previously reported that peptidoleukotrienes, LTC4, LTD4, and LTE4 alter regional blood flow in a divergent manner. Thus, in the anesthetized dog, these substances produced marked intestinal vasoconstriction, but had little to no effect in the kidney. Subsequently, we observed that both LTD4 and LTC4 produced relaxation of isolated superior mesenteric and renal arteries in an apparently endothelial-dependent manner. These observations led to the present proposed research project whole major goal is to comprehensively evaluate these findings and to test the general hypothesis that enhanced levels of peptide leukotrienes, whether of local or remote origin, participate in control of distribution of regional blood flow. These studies will focus primarily on the mesenteric and renal vascular beds. Experiments described will utilize both in vivo and in vitro models. The in vivo experiments will be conducted in anesthetized dogs under conditions of natural blood flow. Regional flow will be measured with noncannulating electromagnetic flow probes. In vitro studies will be conducted on superior mesenteric and renal arterial segments obtained from dogs. In addition, as studies progress, other blood vessels obtained from dogs as well as other species will be investigated. These studies will comprehensively define both hemodynamic and vascular smooth muscle influences of leukotrienes as well as relationships of these products to other vasoactive hormone systems. Overall knowledge gained from these studies will improve our understanding of the potential role of these potent endogenous substances in regulation of the peripheral vascular bed. Enhanced knowledge of peripheral hemodynamic control mechanisms will provide insights into treatment of diseases such as essential hypertension.

花生四烯酸至少是常见的天然前体 两个具有生物活性的化合物家族。 新陈代谢 花生四烯酸通过环氧合酶途径产生双烯酸 前列腺素、前列环素和血栓素，而衍生物 通过 5'-脂氧合酶途径形成的包括氢过氧酸， 羟基酸和白三烯（LT）。 众所周知， 花生四烯酸的血管活性取决于转化为 活性代谢物。 尽管环氧合酶产品已 经过广泛研究，白三烯化合物家族是 最近的发现以及这些产品对区域的影响 血流量和血管舒缩张力尚未明确。 沿着 这些研究的长期目标是增强我们对 白三烯与区域血流动力学控制的关系。 我们之前报道过肽白三烯、LTC4、LTD4、 LTE4 以不同的方式改变局部血流。 因此， 在麻醉狗体内，这些物质产生了明显的 可以使肠道血管收缩，但对肠道血管的影响很小，甚至没有影响。 肾。 随后，我们观察到 LTD4 和 LTC4 都产生了 松弛孤立的肠系膜上动脉和肾动脉 显然是内皮依赖性方式。 这些观察导致 目前提出的研究项目的整个主要目标是 综合评估这些发现并测试一般性 假设增加肽白三烯的水平，是否 本地或远程来源，参与分发控制 局部血流量。 这些研究将主要集中于 肠系膜和肾血管床。 所描述的实验将 利用体内和体外模型。 体内实验 将在自然条件下对麻醉狗进行 血流（量。 区域流量将采用非空管测量 电磁流量探头。 将进行体外研究 肠系膜上动脉和肾动脉段 狗。 此外，随着研究的进展，其他血管 从狗以及其他物种身上获得的病毒将受到调查。 这些研究将全面定义血流动力学和 白三烯对血管平滑肌的影响 这些产品与其他血管活性激素的关系 系统。 从这些研究中获得的总体知识将得到提高 我们对这些有效内源性潜在作用的理解 调节外周血管床的物质。 增强型 了解外周血流动力学控制机制将提供 对原发性高血压等疾病治疗的见解。