Browsing by Subject "dynamic exercise"

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Alterations in Beta-Adrenergic Receptor Density on Human Lymphocytes in Response to Chronic Exercise
(2000-12-01) Brittain, Adam K.; Raven, Peter B.; Grant, Stephen R.; Martin, Michael W.
A number of cardiovascular adaptations have been shown to occur in healthy individuals as a result from regular, chronic exercise training. These changes include, but are not limited to, a lower resting heart rate, a lower heart rate at any given submaximal workload, an increase in stroke volume, an increase in maximal cardiac output due primarily to an increase in contractility, a decreased peripheral vascular resistance (increased peripheral vascular conductance), an overall increase in vascularity, an increase in left ventricular mass, and an increase in total body oxygen extraction (Raven, 1994). Some of these adaptations are also known to commonly occur in patients with coronary artery disease enabling them to increase their total work capacity. Therefore, exercise apparently adapts the heart to better cope with the adverse affects of coronary artery disease and helps to prevent the aforementioned disease from developing in healthy individuals. The beta-adrenergic receptor (β-AR) is essential for the activation of many aspects of the cardiovascular system during dynamic exercise (1). The catecholamines epinephrine and norepinephrine are released from the adrenal medulla and postganglionic fibers of the sympathetic nervous system respectively in response to dynamic exercise. Epinephrine and other beta-adrenergic receptor agonists bind and activate the β-AR on the cell membrane thus allowing it to couple with the stimulatory GTP-binding regulatory protein Gs. This step initiate the activation of adenylate cyclase and the synthesis of cyclic adenosine 3’,5’ monophosphate (cyclic AMP), a key intracellular second messenger. Cyclic AMP ultimately activates cyclic AMP-dependent protein kinase (PKA), an enzyme that phosphorylates a number of intracellular proteins that subsequently influence cell metabolism and function. Alterations in the activity of the adrenergic system seen in several clinical and physiological situations, including exercise, are directly associated with changes in lymphocytic β-AR density or function (2). Moreover, it has been suggested that the changes in receptor density on lymphocytes correlate closely with cardiovascular responsiveness to catecholamines in humans (3-6). Additionally, changes in catecholamine concentration within the physiological range have a regulatory effect on β-AR density and function (7). One particular study established an inverse relationship between plasma and urine catecholamine concentrations and lymphocytic β-AR density in man (8). It is the intent of this review to describe some of the cardiovascular adaptations that occur as a result of chronic exercise and how these changes could be caused by alterations in β-AR density and responsiveness. Additionally, the comparisons and contradictions between chronic heart failure and chronic exercise will be made. The role of the beta-adrenergic system in mediating the effects of exercise will be introduced. The structure of the β-AR will be described and how its molecular structure dictates its function. A brief synopsis will be presented on the mechanism in which β-AR operates subsequent to ligand binding. Alterations of the β-AR, particularly its expression in the heart, through transgenics will then be reviewed to show how this receptor could be responsive for some of the aforementioned adaptations to chronic exercise. In this, some of the differences between the β1- and β2-AR will be described as well as some of the therapeutic implications that could result from overexpression of the β-AR. Following this, alterations in the density of the β-AR after both short-term and long-term exposure to catecholamines will be examined. Included in this section with be the detailed description of the mechanism of receptor desensitization that precedes receptor down-regulation. A brief review will then be given on the effects of chronic exercise on β-AR density. The use of human lymphocytes as model cells will then be described. Binding theory will be explained as it will be the basis of methodology used in any subsequent studies. Along with this, [125 Iodo] cyanopindolol (125I-CYP) will be introduced and its advantages and disadvantages as a β-AR ligand probe will be discussed.
Influence of Thermoregulatory and Nonthermoregulatory Control Mechanisms of Arterial Blood Pressure During Recivert from Exercise in Humans
(2001-05-10) Carter, Robert; Michael L. Smith; Robert L. Kaman; Thomas Yorio
Carter, III Robert, Thermoregulatory and nonthermoregulatory control of arterial pressure during recovery from exercise in humans. Doctor of Philosophy (Biomedical Sciences). May 2001; 153p; 4 tables, 17 figures; 100 titles. The mechanisms of arterial blood pressure control during exercise is well established; however, much less is known about the regulation of arterial blood pressure immediately after intense or prolonged dynamic exercise. Inactive recovery from dynamic exercise is associated with cessation of the primary exercise stimuli from the brain (central command), Skeletal muscle pumping, which contributes to increases in venous return during exercise is also stopped during inactive recovery from exercise. Thus, the skeletal muscle pump and central command each contribute importantly to elevation and maintenance of arterial blood pressure regulation and cerebral blood flow during exercise. When exercise is intense and/or prolonged, the resulting thermal load exacerbates the challenge to maintain arterial blood pressure and cerebral blood flow both during exercise and particularly during recovery from exercise and thereby increases the risk of syncope. Recently, we found that the skeletal muscle pump plays a major role in arterial blood pressure control during recovery from brief (3 min), mild (60% of maximal HR) exercise in which there was no thermal load. However, how the mechanisms of arterial pressure regulation operate during recovery from intense or prolonged exercise when a thermal load occurs is unknown. Therefore, the purpose of the investigations described herein, was to quantify the mechanisms of the carotid baroreflex function, central command, and the skeletal muscle pump when a thermal stress occurs on arterial blood pressure regulation during recovery from exercise in humans. In addition, differences in arterial blood pressure regulation in women and men during recovery from exercise were addressed in women and men. To investigate these mechanisms, we investigated the carotid-cardiac baroreflex function, cardiovascular, and thermoregulatory responses in volunteer subjects during inactive and active recovery from prolonged exercise improved the function of the baroreflex by increasing the functional reserve of the reflex to buffer against hypotensive stimuli. Our data also suggest that thermoregulatory factors contribute to decreases in MAP after inactive recovery from exercise. In addition, the metabolic state of skeletal muscle during longer duration exercise (15 min) may contribute to these responses during inactive recovery from exercise. These results support the hypothesis that thermal stress contributes to the rapid decreases in arterial blood pressure during inactive recovery following dynamic exercise. To investigate gender differences in arterial pressure regulation during recovery from exercise, we compared 11 women and 8 men during 3 min of exercise and 5 min of inactive and active recovery from exercise. Interestingly, at 1 minute after exercise, MAP decreased less during inactive recovery in men when compared to women. This difference was due to greater decreases in SV and less increase in TPR during inactive recovery from exercise in women compared to men. MAP decreased less during active recovery in men when compared to women. These findings suggest that women may have increased risk of post-exercise orthostatic hypotension and that active recovery from exercise may reduce this risk.
Resetting of the Carotid Arterial Baroreflex during Dynamic Exercise
(1997-08-01) Bryant, Kristin Hannah Norton; Peter B. Raven; James Caffrey; Thomas Yorio
Byrant, Kristin, Resetting of the Carotid Arterial Baroreflex during Dynamic Exercise Doctor of Philosophy (Biomedical Sciences), August, 1997; 121 pp; 8 tables; 20 figures, bibliography, 82 titles. Following the initial response to the onset of dynamic exercise, prolonged exercise at a constant workload is characterized by a progressive decrease in stroke volume (SV) and mean arterial pressure (MAP) and concomitant rise in heart rate (HR). These data raise the question as to whether there is a loss of baroreflex regulation of arterial blood pressure during prolonged dynamic exercise. However, we propose that the carotid barareflex (CBR) is continually reset during prolonged exercise, with the operating point being shifted toward the reflex threshold, in relation to a progressive increase in central command activity as motor fibers are recruited in response to muscle fatigue. Therefore, the baroreflex is unresponsive to the fall in MAP. In order to investigate the hypothesis, volunteer subjects performed one hour of dynamic leg cycling exercise at 65% of maximal oxygen uptake (VO2max) with: I) no intervention; and ii) maintenance of cardiac filling volume via continuous infusion of a 6% dextran in saline solution to counteract the fall in SV. At 10 and 50 minutes of exercise, CBR stimulous-response curves were generated using the neck pressure/neck suction technique. The maintenance of cardiac filling volume and thus SV resulted in a diminished drift in MAP. However, indices of central command such as HR, VO2 and ratings of perceived exertion (RPE) increased to the same extent regardless of exercise condition. Furthermore, there was augmented resetting of the CBR at 50 minutes of exercise as compared to 10 minutes under both exercise conditions. In order to further investigate the effects of central command on baroreflex control of blood pressure, a second investigation was designed to demonstrate the effects of exercise type and intensity on CBR function. Stimulus-response relationships were compared during dynamic exercise at a wide range of exercise intensities performed with either leg exercise alone or leg exercise combined with arm exercise. Increases in exercise intensity to maximal exercise resulted in increases in indices of central command such as HR and VO2 as well as an augmentation of the magnitude of the lateral shift in the CBR stimulus-response curve (with the operating point being shifted further toward the threshold of the reflex) relative to the activation of central command. In addition, the performance of combined arm and leg exercise elicited an augmented shift in the carotid-vasomotor stimulus-response relationship as compared to leg exercise alone at the same exercise intensity. As arm exercise compared to leg exercise performed at the same absolute VO2 results in an increased lactate accumulation in the venous system, the augmented resetting of the CBR is likely due to a disproportionate activation of the muscle metaboreflex component of the muscle pressor reflex. Therefore we propose that the central command is the primary mechanism by which the CBR is reset at the onset of dynamic exercise through feed-forward control. However, additional, feed-back modulation can be exerted by the muscle pressor reflex upon the development of mechanical or chemical error signals in the exercising muscle.