HEMODYNAMICS AND VASOACTIVITY IN RENAL 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 导致这些血流动力学的物理因素。主要假设 需要测试的是：1)血管结构变化在 即使在高血压的早期阶段也有升高的阻力；2)有 重要的非压力相关因素对心血管增厚的影响 这些影响包括体液因素和生长发育。 由血管壁细胞产生的因子；以及4)水平升高 内源性循环心脏苷样因子在高血压中的作用 对心血管生长有主要促进作用的药物。 具体目标是：1)进一步对相关角色进行定性评估 早期和慢性血管结构和功能改变的研究 容量扩张型高血压分期：2)进一步量化评估 血管形态和生化的非压力相关变化 3)探索与高血压有关的体液物质 高血压的心血管生长；4)生长因子的探索 高血压时由血管壁组织或相关细胞产生；以及 5)多胺生物合成与多胺代谢关系的研究 内源性钠钾泵抑制剂对高血压患者心血管生长的影响。 实现这些目标所使用的方法包括：1)测量 耐药性、去甲肾上腺素剂量反应曲线和哇巴因诱导的漂移 在这些曲线中，最大限度地扩张血管，泵灌(血)后肢 大鼠血管床；2)水分变化的测量，干燥 心血管组织的重量和定量形态计量学；3)组织 血清和血浆中体液和/或内皮细胞的培养检测 细胞生长因子。 识别促进心血管疾病的非压力相关因素 高血压的室壁增厚将带来新的治疗方法。 如果高血压患者的血管壁增厚能够被预防或减轻， 高血压很可能是无法持续的。

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.