BLOOD VOLUME AND VENOUS RETURN IN THERMAL STRAIN

揭示血浆容量的机制 随着训练而发生的扩展是主要的长期目标， 这一更新申请。 血浆体积膨胀提供了 维持足够的静脉回流，因此维持 热应变条件下的动脉血压。 研究这些 我们已经开发出一种高强度的运动模型， 运动后24小时血浆容量增加10.5%。 我们 我打算为运动大鼠开发一个类似的模型， 研究相关的细胞和器官系统机制。 我们的具体目标是：（1）完善我们的人类模型， 通过频繁测量血液来研究血浆体积膨胀 和尿量和成分的变化超过72小时后， 锻炼的 在这个模型中，我们将检验以下假设：（i）A CP压力反射敏感性的降低先于血容量扩张， 从而允许膨胀的体积保留在血管中 车厢 我们将比较血浆容量和CP压力反射敏感性 在从剧烈运动中恢复的过程中频繁地进行测试。 (ii)强烈刺激后血浆白蛋白含量最初（1-2小时）升高， 运动是间质起源，随后（24小时）升高， 血浆白蛋白含量是由于肝白蛋白合成增加 率 我们将使用稳定同位素方法来测量 血浆容量过程中白蛋白合成速率和白蛋白分布 扩张期。(iii)肾脏对游离水的清除率降低 和溶质在血浆体积膨胀期间， 运动（最多72小时）。 我们将确定水的减少是否 溶质清除是由于醛固酮的作用增加， 抗利尿激素（AVP）。(iv)剧烈的运动刺激会导致 与条件相比，增加口渴感并改善对Na+的适口性 其中血浆渗透压增加而不剧烈运动，因此 促进更快速的再水合。 我们将研究口渴， 不同方案中Na+的适口性。(2)培育出一种动物 用于研究血浆体积膨胀的模型。我们打算使用一个 运动大鼠模型，根据其他人的示范， 增加跑台运动后的血浆容量。 有了这个模型，我们将 测试以下假设：（i）血浆容量扩张， 剧烈运动在很大程度上是由白蛋白合成增加引起的 以及其在血管室中的积聚。 我们将测量 直接合成白蛋白。(ii)一定的盐和水的保留 激素导致原位灌注肝脏中白蛋白合成增加 准备. 我们将测量恢复期动物的白蛋白合成 在肝脏灌注期间， （iii）增加的白蛋白合成， 剧烈运动是由于TI）增加肝白蛋白mRNA可用于 翻译. 我们将测量肝白蛋白mRNA作为 总mRNA，使用翻译测定，在不同时间之前和 在老鼠完成了一个高强度的运动方案后。

Uncovering the mechanisms accounting for the plasma volume expansion that occurs with training is the primary, long-term goal of this renewal application. Plasma volume expansion provides for the maintenance of an adequate venous return, and therefore maintenance of arterial blood pressure in conditions of thermal strain. To study these mechanisms in humans, we have developed an intense exercise model that produces a 10.5% expansion of plasma volume 24 h after exercise. We intend to develop an analogous model for the exercising rat, enabling us to investigate the relevant cellular and organ system mechanisms. Our specific aims are: (1) To refine our human model for the study of plasma volume expansion by making frequent measurements of blood and urine volume and constituent changes over 72 h following intense exercise. With this model, we will test the following hypotheses: (i) A reduction in CP baroreflex sensitivity precedes blood volume expansion, thereby allowing the expanded volume to be retained in the vascular compartment. We will compare plasma volume and CP baroreflex sensitivity at frequent intervals during recovery from intense exercise to test this. (ii) An initial (1-2 h) elevation in plasma albumin content after intense exercise is of interstitial origin and the subsequent (24 h) elevation in plasma albumin content is due to increased hepatic albumin synthetic rate. We will use stable isotopic methodology to measure changes in albumin synthetic rate and albumin distribution during the plasma volume expansion period. (iii) There is a reduced renal clearance of free water and solutes during the plasma volume expansion period following intense exercise (up to 72 h). We will determine whether the reduction in water and solute clearance is due to increased action of aldosterone and antidiuretic hormone (AVP). (iv) The intense exercise stimulus will cause increased thirst and improved palatability to Na+ compared to conditions in which plasma osmolality increases without intense exercise, thus promoting a more rapid rehydration. We will examine thirst and palatability to Na+ in different protocols. (2) To develop an animal model for the study of plasma volume expansion. We intend to use an exercising rat model, based upon the demonstrations of others that rats expand plasma volume after treadmill running. With this model, we will test the following hypotheses: (i) Plasma volume expansion following intense exercise is in large part caused by increased albumin synthesis and its accumulation in the vascular compartment. We will measure albumin synthesis directly. (ii) Certain of the salt and water retention hormones cause increased albumin synthesis in an in situ, perfused liver preparation. We will measure albumin synthesis in animals recovering from intense exercise during liver perfusion with appropriate doses of renin, AVP and aldosterone, (iii) Increased albumin synthesis following intense exercise is due ti) increased hepatic albumin mRNA available for translation. We will measure hepatic albumin mRNA as a percentage of total mRNA, using a translation assay, prior to and at various times after rats have completed an intense exercise protocol.