PERIPHERAL VASCULAR CONTROL MECHANISMS

外周血管控制机制

• 批准号: 3346586
• 负责人: BARRY M CHAPNICK
• 金额: $ 15.02万
• 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 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346586
• 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.

花生四烯酸作为至少一种天然前体， 两类生物活性化合物。 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）。 非常确定的是 花生四烯酸的血管活性依赖于转化为 活性代谢物 虽然环氧合酶产品已经 广泛研究，白三烯家族的化合物是 最近的发现，以及这些产品对区域的影响 血流量和血管张力还没有很好地建立起来。 很长 这些研究的长期目标是提高我们对 白三烯与局部血流动力学控制的关系。 我们以前曾报道过，肽白细胞三烯，LTC 4，LTD 4， 和LTE 4以不同的方式改变局部血流。 因此，在本发明中， 在麻醉的狗，这些物质产生标记 肠血管收缩，但对 肾 随后，我们观察到LTD 4和LTC 4都产生了 离体上级肠系膜动脉和肾动脉舒张 明显的内皮依赖性。 这些观察导致 目前提出的研究项目的主要目标是 全面评估这些发现，并测试一般 假设增强的肽白三烯水平，无论 本地或远程来源，参与控制分配 局部血液流动。 这些研究将主要集中在 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 将在自然条件下在麻醉犬中进行 血流 将使用非插管测量局部血流 电磁流量探头 将进行体外研究 在从以下获得的上级肠系膜和肾动脉段上 狗 此外，随着研究的进展，其他血管 将研究从狗以及其他物种获得的。 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提高 我们对这些强大的内源性的潜在作用的理解 调节外周血管床的物质。 增强 外周血液动力学控制机制的知识将提供 对治疗原发性高血压等疾病的见解。