PERIPHERAL VASCULAR CONTROL MECHANISMS

花生四烯酸至少是一种常见的天然前体 两类具有生物活性的化合物。新陈代谢 花生四烯酸通过环氧合酶途径产生二烯酸 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依赖于转化为 活性代谢物。尽管环氧合酶产品已经被 经过广泛研究，白三烯类化合物是 更新的发现，以及这些产品对地区的影响 血液流动和血管舒缩张力还没有得到很好的确立。一个很长的 这些研究的学期目标是增进我们对 三叉三烯与局部血流动力学控制的关系。 我们之前已经报道过多肽优三烯、LTC4、LTD4、 LTE4以不同的方式改变局部血流量。因此， 在麻醉的狗身上，这些物质产生了明显的 肠血管收缩，但对小鼠的影响很小或没有 肾脏。随后，我们观察到LTD4和LTC4都产生了 离体肠系膜上动脉和肾动脉的松弛 一种明显依赖内皮细胞的方式。这些观察结果导致了 对目前提出的研究项目的全部主要目标是 全面评估这些发现，并测试一般 假设多肽白三烯水平升高，是否 本地或远程来源的，参与控制分发 区域血流量的变化。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。活体实验 将在麻醉犬体内进行，在自然条件下 血液流动。区域流量将采用非插管测量 电磁流量探头。将进行体外研究 肠系膜上动脉和肾动脉节段的研究 狗。此外，随着研究的进展，其他血管 将对从狗和其他物种获得的病毒进行调查。 这些研究将全面定义血液动力学和 白三烯对血管平滑肌的影响 这些产物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改善 我们对这些强大的内源性物质的潜在作用的理解 调节外周血管床的物质。增强版 外周血流动力学控制机制的知识将提供 对原发性高血压等疾病的治疗有独到见解。

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.