It is becoming more apparent that with advancing age there is a reduction/breakdown in homeostatic mechanisms. The nervous and endocrine systems are the primary regulatory pathways responsible for maintaining homeostasis under stressful situations (physical exertion, environmental stimulus, etc). The catecholamines play an integral role in these adaptive processes as epinephrine is a powerful regulator of a number of metabolic and physiologic functions, and norepinephrine reflects the actions of the sympathetic nervous system. There is accumulating evidence suggesting that the ability to produce and respond to catecholamines declines with advancing age, however, mechanisms responsible for such alterations remain unknown. Further, as the homeostatic regulatory systems are actively stimulated/recruited during a bout of acute exercise, the possibility exists that a program of regular exercise, which chronically stresses these systems, may attenuate the observed age-related decline in function. Such a training adaptation would allow the elderly individual to better adapt to stressful situations while being less susceptible to injury. It is the purpose of this proposal to examine the age-related alterations in cardiac tissue of the rat as measured by its ability to: 1) remove and synthesize epinephrine (E) and norepinephrine (NE) at rest and in response to the stress of physical exercise; 2) functionally respond to various doses of NE and/or isoproterenol as measured by changes in maximal rate of tension development (dT/dt), active tension, contraction duration and overall contractility; 3) determine the response of the myocardium to varied concentrations of calcium and 4) determine beta- adrenergic receptor number, density and affinity. Further, in order to assess any beneficial adaptations associated with physical training in the older populations, the animals will be trained by 10 weeks of treadmill running at 75% of their maximal functional capacity. The variables listed above will be measured in these animals and comparisons made with the untrained animals as well as with increasing age.
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