HYPERTENSION AND HYPERTROPHY IN THE NON-HUMAN PRIMATE

非人类灵长类动物的高血压和肥大

• 批准号: 3345600
• 负责人: Richard A. Walsh
• 金额: $ 23.14万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3345600
• 关键词: adenosinetriphosphatase; cineangiocardiography; disease /disorder model; echocardiography; heart contraction; heart dimension /size; intracardiac pressure; intracardiac volume; isozymes; neurohormones; remission /regression; renal hypertension; ventricular hypertrophy

The major objective of this research proposal is to define the fundamental mechanical, neurohumeral and biochemical properties of left ventricular pressure overload hypertrophy and hypertrophy regression in a unique model of experimentally induced renal hypertension in the nonhuman primate (baboon, papio anubis). Our working hypothesis is that longitudinal studies of systolic function using end systolic stress-volume, stress-length and stress-velocity relations and of diastolic function using quantitation of ventricular chamber and myocardial stiffness will identify which characteristics of left ventricular performance herald the onset of contractile depression. Using this approach, we propose to test the following specific hypotheses: 1) That myocardial contractile depression in pressure overload hypertrophy is manifest by either a rightward parallel shift and/or a depression in the slope of the left ventricular force-length relation. 2) That a decrease in the ratio of left ventricular mass to volume or thickness to dimension will be an early marker for contractile depression. 3) That augmented myocardial stiffness in pressure overload hypertrophy unlike chamber stiffness will not occur in the absence of increased myocardial collagen content. 4) That regression of hypertrophy will be accompanied by unaltered contractile function, reduced chamber stiffness and variable effects upon myocardial stiffness. 5) That heterogeneity in the magnitude of hypertrophy in response to hypertension of similar severity and duration may relate to differences in the modulation of the hypertrophy process by the renin-angiotensin and sympathetic nervous systems. 6) That alterations in primate myosin ATPase activity and/or isoenzyme patterns will be an early and sensitive marker of contractile depression. The following specific studies are designed to answer these hypotheses: chronically hypertensive (2-4 years) baboons with LV hypertrophy and variable systolic function will be studied during the progression of hypertrophy and during hypertrophy regression produced by methyldopa. Serial biplane LV cineangiography/M-mode echocardiography with high fidelity pressure measurement will be used to assess serial alterations in end-systolic circumferential/meridional stress-volume/dimension relations and diastolic properties. Plasma renin, catecholamines and vasopressin levels plus baroreceptor function will be measured in the conscious state. Myocardial tissue hydroxyprolene and myosin ATPase will be assayed at necropsy. It is anticipated this multidisciplinary approach will provide basic insights into the determinants of the evolution and regression of pressure overload hypertrophy in an animal model phylogenetically close to man.

本研究计划的主要目标是定义基本原理 左心室的机械、神经体液和生化特性 独特模型中的压力超载肥大和肥大回归 非人类灵长类动物实验诱导肾性高血压的研究 （狒狒、狒狒阿努比斯）。 我们的工作假设是纵向 使用收缩末期压力体积研究收缩功能， 应力-长度和应力-速度关系以及舒张功能使用 心室室和心肌僵硬度的定量将确定 左心室性能的哪些特征预示着 收缩性抑制。 使用这种方法，我们建议测试 以下具体假设：1）心肌收缩抑制 在压力超负荷时，肥大表现为向右平行 左心室力长度斜率的变化和/或下降 关系。 2）左心室质量与左心室质量之比下降 体积或厚度尺寸将是收缩的早期标志 沮丧。 3）压力超负荷时心肌僵硬度增加 与心室僵硬不同的肥厚在没有 心肌胶原含量增加。 4）肥大的回归 将伴随着收缩功能不变、腔室缩小 硬度和对心肌硬度的不同影响。 5）那个 高血压引起的肥大程度的异质性 相似的严重程度和持续时间可能与 肾素-血管紧张素对肥大过程的调节 交感神经系统。 6) 灵长类肌球蛋白 ATP 酶的改变 活性和/或同工酶模式将是早期且敏感的标记 收缩性抑制。 以下具体研究旨在 回答这些假设： 患有慢性高血压（2-4 岁）的狒狒 左室肥厚和可变收缩功能将在研究期间进行研究 肥大的进展和肥大消退期间产生的 甲基多巴。 串行双平面 LV 电影血管造影/M 型超声心动图 高保真压力测量将用于评估串行 收缩末期周向/经向变化 应力-体积/尺寸关系和舒张特性。 血浆肾素， 儿茶酚胺和加压素水平加上压力感受器功能将 在有意识的状态下测量。 心肌组织羟丙烯和 肌球蛋白 ATP 酶将在尸检时进行测定。 预计这 多学科方法将提供基本见解 压力过载演变和回归的决定因素 动物模型中的肥大在系统发育上与人类接近。