PERIPHERAL VASCULAR CONTROL MECHANISMS

外周血管控制机制

• 批准号: 3346589
• 负责人: BARRY M CHAPNICK
• 金额: $ 9.93万
• 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 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346589
• 关键词: gastrointestinal circulation; hemodynamics; hypertension; kidney circulation; leukotrienes; lipoxygenase; 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 prostaglandins, prostacyclin and thromboxane, whereas derivatives formed via the 5'-lipoxygenase pathway include hydroperoxy acids, hydroxy acids and leukotrienes (LT). It is well-established that vosactivity 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 are not well-established. A long-term goal of these studies is to enhance our knowledge of the relationships of leukotrienes 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, in a preliminary investigation, we observed that LTD4 produced relaxation of isolated superior mesenteric and renal arteries in an apparently endothelial-dependent manner. These observations led to the present proposed research project whose major goal is to comprehensively evaluate these findings and to test the general hypothesis that enhanced levels of peptide leukotrines, whether of local or remote origin, participate in control of distribution of regional blood flow. These studies will focus primarily on the mesentric 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 comprenhensively define both hemodynamic and vascular smooth muscle influences of leukotrienes as well as relationships of these products to other vasoactive hormonal 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.

花生四烯酸作为至少两种维生素C的共同天然前体， 生物活性化合物的家族。 花生四烯酸通过 环加氧酶途径产生双烯类胡萝卜素， 前列环素和血栓素，而通过 5 '-脂氧合酶途径包括氢过氧酸、羟基酸和 白三烯（LT）。 众所周知，花生四烯酸 酸依赖于转化成活性代谢物。 虽然 环氧合酶产物已被广泛研究， 家族的化合物是最近发现的，这些化合物的影响 关于局部血液流动的产品还没有很好地建立。 一个长期目标 这些研究的目的是为了提高我们的知识， 白三烯控制局部血流动力学。 我们以前曾报道过肽白三烯，LTC 4，LTD 4和LTE 4， 以不同的方式改变局部血流。 因此，在麻醉的 狗，这些物质产生显着的肠道血管收缩，但有 对肾脏几乎没有影响。 随后，在初步 研究中，我们观察到LTD 4产生了孤立的 肠系膜上上级动脉和肾动脉 内皮依赖性 这些观察导致了目前 建议的研究项目，其主要目标是全面评估 这些发现，并测试一般假设，提高水平的 无论是本地或远程来源的肽白细胞三醇， 控制局部血流的分布。 这些研究将重点 主要在系膜和肾血管床上。 述实验 将利用体内和体外模型。 体内实验 将在自然血液条件下在麻醉犬中进行 流 将使用非插管电磁测量局部血流 流量探头 将对上级肠系膜和 从狗获得的肾动脉段。 此外，作为研究 进展，从犬以及其他物种获得的其他血管 将进行调查。 这些研究将全面地定义这两个 血液动力学和血管平滑肌影响 这些产品与其他血管活性激素系统的关系。 从这些研究中获得的总体知识将提高我们的理解 这些有效的内源性物质在调节中的潜在作用 周围血管床的边缘 增强对外围设备的了解 血液动力学控制机制将为治疗 原发性高血压等疾病。