BEHAVIORAL TREATMENT OF RAYNAUD'S PHENOMENON

我们最近已经证明了雷诺氏病的血管痉挛发作 尽管手指神经阻滞，但仍可能引起疾病， 冷却导致α-肾上腺素能反应增加， 正常志愿者。 为了更精确地确定 原发性雷诺病，有必要确定是否 α 1受体、α 2受体或两者的异常， 血管痉挛发作所必需的。 我们建议 通过动脉内输注α 1拮抗剂来研究这个问题， α 2拮抗剂和两种拮抗剂，同时用 环境和局部冷却（研究1）。 因为我们的调查 迄今为止使用的合成肾上腺素能药物， 雷诺氏病发作中的内源性血管收缩化合物 由于去甲肾上腺素在外周血管 肾上腺素受体，我们建议研究其在冷却和非冷却的影响， 雷诺病患者和对照组的手指（研究2）。 我们已经确定了异常的α-肾上腺素能受体， 雷诺氏病患者，最近表现出家族性 这种疾病的聚集。 由于α-肾上腺素能受体 基因控制，我们建议看看这些基因的突变是否 参与雷诺病的发生（研究5）。 我们已经证明，反馈诱导的血管舒张部分是由 非神经β肾上腺素能血管舒张机制，而不是通过 血浆儿茶酚胺的变化。 一种β肾上腺素能血管扩张剂 与反馈诱导的血管舒张具有相同时程的机制 最近在血管内皮上得到证实。 我们建议 确定血管内皮参与反馈诱导的 使用特异性抑制内皮细胞的化合物进行血管舒张， 介导的血管舒张（研究3）。 尽管对温度生物反馈的研究很多，但几乎没有什么进展 对大脑机制的影响 一种新的MRI（磁共振成像） 该方法允许无创测量脑血流量， 出色的空间和时间分辨率。 我们建议测量大脑 在温度反馈训练之前和之后通过MRI测量血流，或者 可靠的控制程序（研究4）。

We have recently demonstrated that the vasospastic attacks of Raynaud's disease can be provoked despite digital nerve blockade and that local cooling produces increases in alpha-adrenergic responsiveness not found in normal volunteers. To more precisely determine the etiology of primary Raynaud's disease, it is necessary to determine whether abnormalities of alpha1 receptors, alpha2 receptors, or both are necessary for the occurrence of a vasospastic attack. We propose to examine this question by infusing intraarterially an alpha1 antagonist, an alpha2 antagonist, and both antagonists while provoking attacks with environmental and local cooling (Study 1). Since our investigations have thus far utilized synthetic adrenergic drugs it is important to determine the endogenous vasoconstrictive compound involved in Raynaud's attacks. Since norepinephrine is highly potent at peripheral vascular adrenoceptors, we propose to study its effects in cooled and uncooled fingers of Raynaud's disease patients and controls (Study 2). We have identified abnormalities of alpha-adrenergic receptors in Raynaud's disease patients and have recently demonstrated familial aggregation of this disorder. Since alpha-adrenergic receptors are under genetic control, we propose to see if mutations of these genes are involved in the occurrence of Raynaud's disease (Study 5). We have shown that feedback-induced vasodilation is mediated in part by a nonneural beta-adrenergic vasodilating mechanism and not through changes in plasma catecholamines. A beta-adrenergic vasodilating mechanism having the same time course as feedback-induced vasodilation has recently been demonstrated on vascular endothelium. We propose to determine the involvement of vascular endothelium in feedback-induced vasodilation using a compound that specifically inhibits endothelium- mediated vasodilation (Study 3). Despite much research on temperature biofeedback, little has been done on the brain mechanisms involved. A new MRI (magnetic resonance imaging) method permits the noninvasive measurement of brain blood flow with excellent spatial and temporal resolution. We propose to measure brain blood flow by MRI before and after training in temperature feedback or a credible control procedure (Study 4).