ENDOTHELIUM-DEPENDENT CONSTRICTION IN HYPERTENSION

内皮细胞释放舒张因子（EDRF），其中一氧化氮 (NO)似乎是最重要的。 内皮依赖性舒张 在高血压动物的动脉中减少。 自发性 高血压大鼠（SHR），这已被归因于生产的一个 尚未鉴定的内皮源性收缩因子（EDCF）。 的 建议的研究将确定EDRF和EDCF之间的相互作用， 并确定后者是否是内过氧化物。 我们还将 试图确定血小板衍生产品或内皮素是否可以 被认为是释放EDCF的（病理性）生理刺激。 我们 将开始探索分子生物学方面， EDCF的生产。 我们将探讨是否内皮依赖性 收缩在另一种遗传性高血压模型中是突出的， 新西兰遗传性高血压大鼠 我们将研究 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。 我们将确定内皮依赖性 收缩可由细胞因子白细胞介素-2诱导。 我们希望 证明EDCF有助于异常反应， 高血压血管不仅引起血管收缩， 通过促进血管平滑肌的生长 我们将使用 已建立的技术，以生物测定释放的承包和 松弛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， 比色法）和放射免疫测定法来确定性质和作用 EDCF和血管平滑肌。 我们将介绍分子 生物技术来确定表达和/或表达的程度， 导致EDCF产生的酶的活性。 这些 研究将使人们深入了解慢性作用的因素释放， 血管内皮和血管平滑肌的病理生理 高血压，并可能有助于解释过渡，从 早期高血压血管收缩阶段的形态 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.