AGING AND CARDIOVASCULAR FUNCTION

已知心血管系统发生重大变化的原因是 衰老。此外，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, 高血压可以被认为是心血管危险因素，因为 卒中和心肌梗死的发病率显著高于 患有高血压的老年人。其背后的机制是 血压的升高尚不清楚，尽管血压的下降 压力感受性反射功能已被牵连。然而，有哪些因素 导致压力感受器反射功能障碍的原因尚不清楚。假设是 测试表明，与年龄相关的心血管功能变化是由于 压力感受性反射功能的改变 内源性阿片类药物。考虑到这一点，这一行动的具体目标是 建议：1)评估压力感受器反射与年龄相关的变化 包括四个年龄组的大鼠的敏感性(Fischer 344只大鼠 6、12、18和24个月)。这将通过首先评估 药物上调清醒完整大鼠的压力感受器 以及降低血压和观察心率变化的反应。 下一步，传入肢体和反射弧的中心部分将 通过电刺激颈动脉窦进行隔离和检查 孤束神经和孤束核；2)评价 内源性阿片类药物在青年和老年人压力反射调节中的作用 老鼠。这将通过操纵内源性阿片类药物的影响来实现。 使用合适的拮抗剂并如上评估压力反射；3) 确定内源性阿片调节作用的中枢部位(S) 通过选择性微量注射特定的激动剂和 拮抗剂进入已知参与心血管系统的区域 调节；4)评估心血管系统 回应挑战。在这种情况下，将使用心理社会压力 诱发高血压及其对压力感受器反射的影响和作用 内源性阿片类药物检查。因此，本文件中描述的实验 应用Win揭示了年龄相关变化的机制 老年人的心血管功能和允许更好的 了解为什么血压会随着年龄的增长而升高。作为一名 结果：最佳治疗方法可选择或采用新的治疗方法 开发用于治疗或预防老年人心血管功能障碍的药物。

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.