PERIPHERAL VASCULAR CONTROL MECHANISMS

花生四烯酸是至少两种物质的共同天然前体 生物活性化合物家族。 花生四烯酸的代谢通过 环氧合酶途径产生双烯前列腺素， 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，花生四烯酸的活性 酸依赖于活性代谢物的转化。 虽然 环氧合酶产品已被广泛研究，白三烯 化合物家族是最近发现的，这些化合物的影响 关于局部血流的产品尚未完善。 长期目标 这些研究的目的是为了增强我们对以下关系的认识： 白三烯控制局部血流动力学。 我们之前报道过肽白三烯、LTC4、LTD4 和 LTE4， 以不同的方式改变局部血流。 因此，在麻醉状态下 狗，这些物质产生显着的肠道血管收缩，但 对肾脏影响很小甚至没有影响。 随后，在初步 调查中，我们观察到 LTD4 产生了孤立的弛豫 肠系膜上动脉和肾动脉明显 内皮依赖性方式。 这些观察结果导致了目前的情况 提出的研究项目，其主要目标是综合评估 这些发现并检验了增强水平的一般假设 肽白三烯，无论是本地来源还是远程来源，都参与 控制局部血流的分布。 这些研究将集中 主要作用于肠系膜和肾血管床。 实验描述 将利用体内和体外模型。 体内实验 将在自然血液条件下对麻醉狗进行 流动。 区域流量将通过非空心电磁测量 流量探头。 体外研究将在肠系膜上层和 从狗身上获得的肾动脉片段。 另外，作为研究 进展，从狗以及其他物种获得的其他血管 将被调查。 这些研究将全面定义 白三烯对血流动力学和血管平滑肌的影响 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。 增强周边知识 血流动力学控制机制将为治疗提供见解 原发性高血压等疾病。

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.