HEMODYNAMICS AND VASOACTIVITY IN HYPERTENSION

这项拟议研究的总体目标是描述 外周血管床在不同阶段的血流动力学状态 实验性高血压，并试图确定化学和/或 造成这些血流动力学的物理因素。 主要假设 测试是：1）血管结构的变化是最重要的， 即使在高血压的早期阶段也会增加阻力; 2） 对心血管壁增厚的重要非压力相关影响 高血压; 3）这些影响包括体液因素和生长 由血管壁细胞产生的因子;和4）存在升高的水平 内源性循环心脏糖苷样因子在高血压中的作用 对心血管生长有主要的热带效应。 具体目标是：1）进一步定性评估的相对作用 早期和慢性的结构和功能性血管变化 容积扩张性高血压的分期; 2）进一步定量评估 非压力相关的血管形态学和生物化学变化 高血压的血管壁; 3）探索与高血压有关的体液物质 高血压心血管生长; 4）生长因子的探索 由高血压中的血管壁组织或相关细胞产生;以及 5)多胺生物合成与 内源性钠钾泵抑制剂对高血压心血管生长的影响。 为实现这些目标而采用的方法包括：1）衡量 阻力、去甲肾上腺素剂量-反应曲线和哇巴因诱导的偏移 在这些曲线中，最大血管舒张，泵灌注（血液）后肢 大鼠血管床; 2）测量含水量变化，干 心血管组织的重量和定量形态学;以及3）组织 体液和/或内皮细胞的血清和血浆组分的培养测定 细胞生长因子 促进心血管疾病的非压力相关因素的识别 高血压室壁增厚将导致新的治疗方法。 如果高血压的血管壁增厚可以预防或减弱， 高血压很可能无法持续。

The general objectives of this proposed research are to describe the hemodynamic state of peripheral vascular beds in the various stages of experimental hypertension, and to attempt to identify the chemical and/or physical factors responsible for these hemodynamics. Major hypotheses to be tested are: 1) vascular structural changes are of primary importance in elevating resistance even in early stages of hypertension; 2) there are important non-pressure-related influences on cardiovascular wall-thickening in hypertension; 3) these influences include humoral factors and growth factors produced by vascular wall cells; and 4) there are elevated levels of endogenous circulating cardiac glycoside-like factors in hypertension that have primary tropic effects on cardiovascular growth. Specific aims are: 1) further qualitative assessment of the relative roles of structural and functional vascular changes in the early and chronic stages of volume-expanded hypertension; 2) further quantitative assessment of non-pressure-related changes in morphology and biochemistry of vascular walls in hypertension; 3) exploration for humoral substances involved in cardiovascular growth in hypertension; 4) exploration for growth factors produced by vascular wall tissues or associated cells in hypertension; and 5) investigation of the relationship of polyamine biosynthesis and endogenous Na-K pump inhibitors on cardiovascular growth in hypertension. Methodology to be used to achieve these aims includes: 1) measurement of resistance, norepinephrine dose-response curves and ouabain-induced shifts in these curves in maximally-vasodilated, pump-perfused (blood) hindlimb vascular beds of rats; 2) measurement of changes in water content, dry weight and quanitiative morphometry of cardiovascular tissue; and 3) tissue culture assay of serum and plasma fractions for humoral and/or endothelial cell growth factors. Identification of non-pressure-related factors promoting cardiovascular wall thickening in hypertension would lead to new therapeutic approaches. If vascular wall thickening in hypertension can be prevented or attenuated, it is likely that the hypertension cannot be sustained.