ENDOGENOUS OPIATES, STRESS AND RISK FOR HYPERTENSION

内源性阿片类药物、压力和高血压风险

• 批准号: 3344196
• 负责人: JAMES A MCCUBBIN
• 金额: $ 13.85万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3344196
• 关键词: autonomic nervous system; baroreceptors; behavior test; blood pressure; cardiovascular disorder diagnosis; cardiovascular disorder prevention; catecholamines; disease /disorder proneness /risk; health behavior; hypertension; muscle relaxation; naloxone; neural information processing; neuropeptide receptor; neuropeptides; physiologic stressor; psychological stressor; relaxation; stress; sympathetic ganglion; young adult human (21-34)

Endogenous opioid peptides comprise an important neuroregulatory mechanism which can centrally integrate autonomic outflow. Young adults at risk for later development of hypertension show a pattern of exaggerated circulatory, sympathoadrenal and behavioral responses in both laboratory and naturalistic settings. Although extreme blood pressure fluctuations in young people may ultimately result in sustained hypertension, the biobehavioral mechanisms of their reactivity remain to be identified. Endogenous opioid peptides are released during behavioral stress and inhibit sympathetic nervous system responses. Their role in control of autonomic outflow and blood pressure has led to the hypothesis that defective opioidergic sympathoinhibition is responsible for blood pressure dysregulation in the early stages of hypertension. We have tested this hypothesis in our lab by examination of the effects of the opiate antagonist, naloxone on blood pressure responses to stress in young adults with high casual blood pressure. Results suggest that opioid inhibition of responses to stress directly influences blood pressure levels and may likewise influence risk for hypertension. Experimental verification of the latter is only now practical because of two recent technological advances. First, development of reliable, accurate, and unobtrusive portable blood pressure monitors now enables reasonable determination of ambulatory pressures in naturalistic settings. Second, recent FDA approval of the long-lasting oral opiate antagonist, Trexan, has made it possible to measure opioidergic influences on blood pressure during normal daily activities. The proposed studies are designed to confirm and extend previous work by examination of two related questions: 1) Does opioid inhibition of laboratory reactivity reflect opioid control of ambulatory pressures in naturalistic settings? 2) Do behaviors which reduce stress reactivity operate via opioidergic mechanisms? These studies are necessary to link existing laboratory findings to the developmental pathophysiology of hypertension so that behavior therapies can be more strategically designed to reduce blood pressure. Increased understanding of potentially therapeutic opioid mechanisms and opio-agonistic behaviors will enable better diagnosis and treatment of mild hypertension.

内源性阿片肽是一种重要的神经调节因子， 可以集中整合自主流出的机制。 年轻人 在高血压后期发展的风险表现出一种模式， 夸大的循环，交感肾上腺和行为反应， 实验室和自然环境。 虽然极端的血液 年轻人的压力波动可能最终导致持续的 高血压，其反应性的生物行为机制仍然是 被识别。 内源性阿片肽在 行为应激和抑制交感神经系统反应。 它们在控制自主神经流出和血压方面的作用导致了 阿片类交感神经抑制缺陷的假设是 在早期阶段的血压失调负责 高血压 我们已经在实验室里通过检验 阿片受体拮抗剂纳洛酮对血压应激反应的影响 在年轻人中偶尔高血压。 结果提示 阿片类药物对应激反应的抑制直接影响血液 血压水平，并可能同样影响高血压的风险。 后者的实验验证现在才实际，因为 两项最新的技术进步 一是发展可靠、 准确、不显眼的便携式血压监测仪现在能够 合理测定自然状态下的动态血压 设置. 其次，最近FDA批准了长效口服阿片类药物， 拮抗剂，Trexan，使测量阿片类药物 在正常的日常活动中对血压的影响。 拟议的研究旨在确认和扩展以前的工作， 检查两个相关问题：1）阿片类药物抑制 实验室反应性反映阿片类药物对 自然环境？ 2)减少压力反应的行为 通过阿片类机制运作 这些研究是必要的联系 现有的实验室研究结果， 这样行为疗法就可以更有策略地 用来降低血压的 更加了解 潜在的阿片类药物治疗机制和阿片类药物激动行为 可以更好地诊断和治疗轻度高血压。