Significant changes in the cardiovascular system are known to occur with aging. Furthermore, it is a fact that approximately 50% of the elderly population over 65 years of age suffer from hypertension. This population makes up 15% of the general population. In addition, hypertension can be considered a cardiovascular risk factor in that the incidence of stroke and myocardial infarction is significantly higher in elderly people with hypertension. The mechanisms underlying the elevation in blood pressure are not clear, although a decrement in baroreflex function has been implicated. However, what factors contribute to baroreflex dysfunction are not known. The hypothesis to be tested is that age-related changes in cardiovascular function are due to alterations in baroreflex function resulting from increased actions of endogenous opioids. With this in mind, the specific aims of this proposal are: 1) to evaluate age-related changes in baroreflex sensitivity in rats encompassing four age groups (Fischer 344 rats at 6,12,18, and 24 months). This will be accomplished by first evaluating baroreceptors in the intact, conscious rat by pharmacologically raising and lowering blood pressure and observing heart rate changes in response. Next, the afferent limb and the central components of-the reflex arc will be isolated and examined via electrical stimulation of the carotid sinus nerve and nucleus tractus solitarius; 2) to evaluate the role of endogenous opioids in the regulation of baroreflexes in young and old rats. This will be done by manipulating endogenous opioid influences with appropriate antagonists and evaluating baroreflexes as above; 3) to determine the central site(s) of action of endogenous opioid modulation of baroreflexes by selectively microinjecting specific agonists and antagonists into regions known to participate in cardiovascular regulation; 4) to evaluate the ability of the cardiovascular system to respond to a challenge. In this case, psychosocial stress will be used to induce hypertension and the effects on baroreflexes and the role of endogenous opioids examined. Thus, the experiments described in this application win shed light on the mechanisms of age-related changes in cardiovascular function in the elderly and allow for a better understanding of why blood pressure becomes elevated with age. As a result, the best treatment may be selected or new therapeutic methods developed to treat or prevent cardiovascular dysfunction in the elderly.
