BEHAVIORAL STRESS AND OPIOID MECHANISMS IN HYPERTENSION

拟议研究的目标是继续主要的 研究人员对改变的阿片能抑制的系统研究 交感神经系统与心血管反应性 行为应激与特发性高血压的发生发展 高血压。阿片类药物对血压的抑制也可能是重要的 在交感神经的降压作用中，行为和 药物疗法。最近的四项发现支持这一观点： 1)阿片类拮抗剂纳洛酮的升压作用是 年轻人在行为应激期间显著减少 高血压风险增加，2)血浆β-内啡肽水平 某些高血压患者组显著降低，3) 可乐定的慢性降压治疗使两者恢复正常 血压和β-内啡肽水平，以及4)抗高血压药物 纳洛酮拮抗可乐定对部分高血压患者的作用 病人。建议进行研究以确定内源性的作用 阿片类药物在高血压病病理生理学中的作用机制 为了研究假想的阿片类药物释放机制在 可乐定降压药物治疗。这将是 通过检查纳洛酮对循环的影响来实现 以及休息时的神经内分泌反应和行为应激 未服药的轻度、无并发症的原发性高血压患者 (与规范控制相比)。纳洛酮的升压作用 在未服用药物的高血压患者的亚组中进行检查 没有交感神经系统过度活跃的迹象。角色 阿片类药物降血压作用机制的研究进展 交感神经降压治疗将通过记录确定 纳洛酮慢性给药后升压效应的变化 可乐定。阿片类药物对血压作用机制的阐明 高血压的调节失调将促进对 诊断、病理生理机制和最佳治疗方法 在这一异质疾病类别中的战略。

The objectives of the proposed research are to continue the Principal Investigator's systematic study of altered opioidergic inhibition of sympathetic nervous system and cardiovascular reactivity during behavioral stress in the development of idiopathic essential hypertension. Opioid inhibition of blood pressure may also be important in the antihypertensive action of sympatholytic behavioral and pharmacological therapies. Four recent findings support this contention: 1) the pressor effect of the opioid antagonist, naloxone, is significantly diminished during behavioral stress in young adults at enhanced risk for hypertension, 2) plasma levels of beta-endorphin are significantly decreased in some groups of hypertensive patients, 3) chronic antihypertensive treatment with clonidine normalizes both blood pressure and beta-endorphin levels, and 4) the antihypertensive effect of clonidine is antagonized by naloxone in some hypertensive patients. Research is proposed to determine the role of endogenous opioid mechanisms in the pathophysiology of essential hypertension and to investigate the role of an hypothesized opioid-releasing mechanism in antihypertensive pharmacotherapy with clonidine. This will be accomplished by examination of the effects of naloxone on circulatory and neuroendocrine responses during rest and behavioral stress in unmedicated patients with mild, uncomplicated essential hypertension (compared with normative controls). The pressor effect of naloxone will be examined in subgroups of unmedicated hypertensive patients with and without signs of excessive sympathetic nervous system activity. The role of opioid mechanisms in the blood pressure-lowering effect of sympatholytic antihypertensive therapy will be determined by documenting changes in the pressor effect of naloxone after chronic medication with clonidine. Elucidation of opioid mechanisms of blood pressure dysregulation in hypertension will advance understanding of the diagnosis, pathophysiologic mechanisms, and optimum therapeutic strategies in this heterogeneous disease category.