DEPENDENT CONSTRICTION IN HYPERTENSION

内皮细胞释放松弛因子(EDRF)，其中一氧化氮 (不)似乎是最重要的。内皮依赖性松弛 在高血压动物的动脉中减少。在不由自主的 高血压大鼠(SHR)这被归因于一种 尚未确定的内皮细胞衍生收缩因子(EDCF)。这个 拟议的研究将确定EDRF和EDCF之间的相互作用， 并确定后者是否是内过氧化产物。我们还将 尝试定义血小板衍生产品或内皮素是否可以 被认为是EDCF释放的(病理性)生理刺激。我们 将开始探索分子生物学方面的基础 EDCF的生产。我们将探索是否依赖于内皮 宫缩在另一种遗传性高血压模型中尤为突出，即 新西兰遗传性高血压大鼠。我们会研究这种可能性 内皮依赖性收缩的发生反映了 暴露于慢性高血压的血管壁过早老化。 我们将确定是否发生内皮依赖性 细胞因子白介素2可以诱导宫缩。我们希望 证明EDCF是导致 高血压血管不仅通过引起血管收缩，而且还通过 通过促进血管平滑肌的生长。我们将使用 建立了生物测定收缩和释放的技术 放松因子和监测细胞生长。我们将使用 常规化学方法(气相色谱-质谱法， 比色法)和放射免疫测定法来确定性质和作用 血管内皮细胞和血管平滑肌的表达。我们将介绍分子 确定表达和/或基因表达程度的生物技术 导致EDCF产生的酶的活性。这些 研究将深入了解由以下因素释放的慢性作用 血管内皮细胞和血管平滑肌在血管病理生理学中的作用 高血压，并可能有助于解释从 血管收缩阶段对早期高血压的形态影响 使高血压过程永久化的适应。

Endothelial cells release relaxing factors (EDRF), of which nitric oxide (NO) appears to be the most important. Endothelium-dependent relaxations are reduced in arteries from hypertensive animals. In the spontaneously hypertensive rat (SHR) this has been attributed to the production of a yet unidentified endothelium-derived contracting factor (EDCF). The proposed research will determine the interactions between EDRF and EDCF, and determine whether or not the latter is an endoperoxide. We will also try to define whether or not platelet-derived products or endothelins can be regarded as (patho) physiological stimuli for the release of EDCF. We will begin to explore the molecular biological aspects that underlie the production of EDCF. We will explore whether or not endothelium-dependent contractions are prominent in another model of genetic hypertension, the New Zealand genetic hypertensive rat. We will examine the likelihood that the occurrence of endothelium-dependent contractions reflects premature aging of the blood vessel wall exposed to chronic hypertension. We will determine whether or not the occurrence of endothelium-dependent contractions can be induced by the cytokine interleukin-2. We hope to demonstrate that EDCF contributes to the abnormal responsiveness of hypertensive blood vessels not only by evoking vasoconstriction but also by facilitating the growth of vascular smooth muscle. We will use established techniques to bioassay the release of contracting and relaxing factors and to monitor cellular growth. We will use conventional chemical methods (gas chromatography-mass spectrometry, colorimetry) and radioimmunoassays to define the nature and the actions of EDCF and vascular smooth muscle. We will introduce molecular biological techniques to determine the degree of expression and/or of activity of the enzymes that leads to the production of EDCF. These studies will give insight into the chronic role of factors released by the endothelium and vascular .smooth muscle in the pathophysiology of hypertension, and may help to explain the transition from the vasoconstrictor stage in early hypertension to the morphological adaptation that perpetuates the hypertensive process.