PERIPHERAL VASCULAR CONTROL MECHANISMS

白三烯（LT）C4和D4是慢反应的主要成分， 过敏物质（SRS-A）。先前的研究结果表明， 这些物质有能力产生内皮依赖性 血管舒张，在动脉中，依赖于 内皮衍生的舒张因子（EDRF）。释放的因子 LTD 4不能通过药理学标准区分动脉 从经典的EDRF，被认为是一氧化氮（NO）或 一种不稳定的亚硝基化合物，释放NO。 观察发现，LTD 4诱导内皮依赖性 以更有力和有效的方式松弛肾静脉，但 血管舒张活性是由于一种机制或介质以外的 花生四烯酸的环氧合酶衍生产物，经典的EDRF/NO， 或血管平滑肌超极化随之而来的ATP敏感 K+通道激活。最近的观察表明， 信号转导途径和可能不同的LT受体可能 解释了这些物质在动脉中的不同活动， 静脉此外，LTC 4和LTD 4均诱发显著的内皮细胞- 内脏电容静脉的依赖性舒张。 这些后者 观察结果似乎与已知的血流动力学变化一致 这发生在过敏性休克，包括低血压和跌倒 与静脉回流减少相关的心输出量 心脏继发于内脏静脉容量血管舒张 脉管系统 正是上述观察结果导致了 制定的工作假设：a）内皮依赖性舒张诱发 在静脉中通过LT是由于一种机制/介质， 位于静脉和动脉上的LT的EDRF/NO和B）受体 内皮细胞不同。为了评估这些假设，研究 拟用于：全面表征血管痉挛的诱发变化 在离体血管环制备中的张力;鉴定和表征， 通过生物测定，来自血管节段或 原代内皮细胞培养;并确定受体结合 内皮细胞膜上LT的特征。整体知识 从这些研究中获得的信息将有助于提高我们对 这些有效的内源性物质在调节血管扩张中的作用 张力和外周血流动力学。

Leukotrienes (LT) C4 and D4 are the principal Components of slow reacting substance of anaphylaxis (SRS-A). Results of previous studies have shown that these substances have the capacity to produce endothelium dependent vasomotor relaxation, which, in arteries, is dependent on the release of an endothelium derived relaxing factor (EDRF). The factor released by LTD4 from arteries could not be distinguished by pharmacological criteria from the classical EDRF, considered to be nitric oxide (NO) or an unstable nitroso compound that releases NO. In contrast to these observations, it was found that LTD4 induced endothelium-dependent relaxation of the renal vein in a more potent and efficacious manner, but the vasorelaxant activity was due to a mechanism or mediator other than cyclooxygenase-derived products of arachidonic acid, the classic EDRF/NO, or vascular smooth muscle hyperpolarization consequent to ATP-sensitive K+ channel activation. More recent observations suggest that multiple signal transduction pathways and perhaps different LT receptors may account for the diverse activity of these substances in arteries and veins. Additionally, both LTC4 and LTD4 evoke marked endothelium- dependent relaxation of visceral capacitance veins. These latter observations appear to be consistent with the known hemodynamic changes which occur during anaphylactic shock, including hypotension and a fall in cardiac output associated with a reduction in venous return to the heart secondary to vasodilation of splanchnic venous capacitance vasculature. It was these aforementioned observations that led to the formulated working hypotheses: a) endothelium dependent relaxation evoked in veins by LTs is consequent to a mechanism/mediator that differs from EDRF/NO and b) receptors for LTs localized on venous and arterial endothelium differ. In order to evaluate these hypotheses, studies are proposed to: comprehensively characterize evoked changes in vasomotor tone in isolated vascular ring preparations; identify and characterize, via bioassay, vasomotor mediators derived from vascular segments or primary endothelial cell cultures; and define receptor binding characteristics of LTs on endothelial cell membranes. Overall knowledge gained from these studies will help to improve our understanding of the role of these potent endogenous substances in the regulation of vasomotor tone and peripheral hemodynamics.