ENDOGENOUS OPIATES, STRESS AND RISK FOR HYPERTENSION

内源性阿片肽是一种重要的神经调节物质 可以集中整合自主流出的机制。青壮年 高血压的未来发展风险显示出一种模式 夸大的循环、交感-肾上腺和行为反应 无论是实验室环境还是自然主义环境。虽然血腥至极 年轻人的压力波动最终可能导致持续的 高血压，其反应的生物行为机制仍然是 被指认出来。内源性阿片肽在体内释放 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 有缺陷的阿片能交感神经抑制存在缺陷的假说 对高血压早期的血压失调负责 高血压。 我们已经在我们的实验室里通过检验效应来检验这一假设 阿片类拮抗剂纳洛酮对血压应激反应的影响 适用于有临时高血压的年轻人。结果表明， 阿片类药物对应激反应的抑制直接影响血液 血压水平，并同样可能影响高血压的风险。 后者的实验验证现在才是可行的，因为 两项最新的技术进步。第一，发展可靠的、 准确、不显眼的便携式血压监测仪现在可以 自然主义运动中动态压力的合理确定 设置。其次，FDA最近批准了这种长效口服阿片类药物 拮抗剂特雷克生使测量阿片类药物成为可能 在日常活动中对血压的影响。 拟议的研究旨在通过以下方式确认和扩展先前的工作 两个相关问题的检验：1)阿片类药物抑制 实验室反应性反映阿片类药物对动态血压的控制 自然主义环境？2)行为会降低应激反应吗？ 通过阿片能机制运作吗？这些研究是必要的，将 现有的实验室发现与发育的病理生理学有关 高血压，使行为治疗更具战略性 旨在降低血压。加深了对 潜在的治疗性阿片机制和阿片激动剂行为 将使轻度高血压得到更好的诊断和治疗。

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.