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.
Showing the most recent 10 out of 41 publications
