ENDOTHELIUM AND VASCULAR RESPONSIVENESS

建议的研究旨在了解 血管反应异质性的潜在机制，这 在正常情况下提供最佳集成 血管系统的功能，而在病理状态下 会导致血管痉挛或高血压疾病。我们将继续 正在进行的关于分离的动脉和静脉的研究 不同的血管床。这项拟议的研究将分析三个 内皮依赖反应性的几个方面。在第一部分中， 我们将尝试找出这种异质性的原因 不同动脉和大静脉在正常情况下的行为 条件。我们将确定异质性是否是由于 通向血管内皮细胞。我们将在 尤其是内皮细胞产生的可能性 几种血管活性因子，以及血管的敏感性 平滑肌到内皮衍生的松弛和收缩 各种因素各有不同。为了研究内皮细胞在血管内皮细胞中的作用 释放放松和收缩因素，我们会比较 有内皮和无内皮的制剂，生物测定法 暴露于内皮细胞的溶液的血管活性特性， 测定花生四烯酸类药物的代谢产物的释放 氨的生产。血管顺应性的研究 肌肉，我们将测量等长张力的变化，细胞 膜电位与环核苷酸的产生。在一个 第二部分，我们将研究生理因素是如何影响 慢性内皮依赖性反应；变量为 研究的是慢性血流改变，肾上腺素能 神经支配、性激素或饮食脂质的变化。在 提案的最后一部分，我们将研究内皮- 冠状动脉各节段的依赖性反应性 曾受过先前伤害的猪，之后 内皮细胞已经再生。脂类改变的后果 摄入量对内皮细胞诱导血管内皮细胞改变能力的影响 还将测试血管平滑肌的收缩性能。 在这个模型中，引起血管反应的刺激中 将特别注意聚集血小板，因为这些 可能在冠状动脉血管痉挛中起关键作用。

The proposed studies are directed to the understanding of the mechanisms underlying heterogeneity of vascular responses, which under normal conditions provides for optimal integration of the functions of the vascular system, whereas in pathological states it can cause vasospasm or hypertensive disorders. We will continue the ongoing studies on isolated arteries and veins taken from different vascular beds. The proposed research will analyze three aspects of endothelium-dependent responsiveness. In a first part, we will attempt to identify the reasons for the heterogeneous behavior of different arteries and large veins under normal conditions. We will determine whether the heterogeneity is due to the endothelium of the smooth muscle. We will examine in particular the possibilities that the endothelial cells generate several vasoactive factors, and that the sensitivity of vascular smooth muscle to endothelium-derived relaxing and contracting factors varies. To examine the role of the endothelium in releasing relaxing and contracting factors, we will compare preparations with and without endothelium, bio-assay the vasoactive properties of solutions exposed to endothelial cells, measure the release of metabolities of arachidonic aid and the production of ammonia. To study responses of vascular smooth muscle, we will measure changes in isometric tension, cell membrane potential and production of cyclic nucleotides. In a second part, we will examine how physiological factors can affect endothelium-dependent responses chronically; the variables to be studied are chronic alterations in blood flow, adrenergic innervation, sex hormones or changes in dietary lipids. In the final part of the proposal, we will study the endothelium- dependent responsiveness of segments of coronary arteries of the pig which have been exposed to a previous injury after which the endothelium has regenerated. The consequences of altered lipid intake on the ability of that endothelium to induce changes in contractility of vascular smooth muscle will be tested also. Among the stimuli causing vascular responses in this model special attention will be paid to aggregating platelets, since these may play a key role in coronary vasospasm.