AGING AND CARDIOVASCULAR FUNCTION

心血管系统的显著变化是已知的， 衰老 事实上，大约50%的老年人 65岁以上的人口患有高血压。 这 人口占总人口的15%。 此外，本发明还提供了一种方法， 高血压可被认为是心血管危险因素， 中风和心肌梗死的发病率明显高于 老年高血压患者。 的作用机制 血压升高尚不清楚，尽管血压下降， 压力感受器反射功能也受到影响。 但是，哪些因素 导致压力反射功能障碍的原因尚不清楚。 假设是 年龄相关的心血管功能变化是由于 压力感受器反射功能的改变， 内源性阿片样物质 考虑到这一点， 建议：1）评估压力感受性反射的年龄相关变化 包括四个年龄组的大鼠（Fischer 344大鼠， 6、12、18和24个月）。 这将通过首先评估 压力感受器在完整的，清醒的大鼠，通过提高 降低血压并观察心率变化。 接下来，传入肢和反射弧的中枢成分将 通过电刺激颈动脉窦进行分离和检查 神经和孤束核; 2）评估的作用， 内源性阿片类物质对青年和老年人压力感受性反射的调节 大鼠 这将通过操纵内源性阿片样物质的影响来实现 与适当的拮抗剂和评价压力反射，如上所述; 3） 确定内源性阿片调节作用的中枢部位 通过选择性地微量注射特定的激动剂， 拮抗剂进入已知参与心血管 调节; 4）评估心血管系统的能力， 回应挑战 在这种情况下，将使用心理社会压力 诱导高血压和对压力感受性反射的影响以及 检查内源性阿片类药物。 因此，本文中描述的实验 的应用，揭示了与年龄有关的变化的机制， 老年人的心血管功能，并允许更好的 了解为什么血压会随着年龄的增长而升高。 作为 结果，可以选择最佳治疗方法或新的治疗方法 开发用于治疗或预防老年人心血管功能障碍。

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.