CATECHOLAMINES AND SEROTONIN IN BLOOD PRESSURE CONTROL

儿茶酚胺和血清素在血压控制中的作用

• 批准号: 3341770
• 负责人: CURT R FREED
• 金额: $ 10.33万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341770
• 关键词: antihypertensive agents; cardiovascular disorder chemotherapy; cardiovascular pharmacology; catecholamines; clonidine; dopamine; electrochemistry; epinephrine; hormone metabolism; hormone regulation /control mechanism; human therapy evaluation; hypotension; norepinephrine; serotonin

Serotonin and the catecholamines are known to play a role in the regulation of blood pressure. Serotonin agonists, alpha-2 receptor agonists and dopamine agonists have all been shown to lower blood in hypertensive animals. Humans with hypertension are routinely treated with clonidine and alpha methyldopa, two drugs which lower blood pressure by central stimulation of alpha-2 adrenoreceptors. Despite the therapeutic success of these drugs, there is no detailed knowledge of how individual brainstem nuclei use norepinephrine, epinephrine, dopamine and serotonin during changes in blood pressure. With the new technique of in vivo electrochemistry, we have been able to follow the time course of catechol and 5-HIAA concentrations continuously during drug- induced hypertension and hypotension. During the first award period of this grant, we found that the serotonin metabolite 5- HIAA was increased in most nuclei whenever blood pressure was increased. The catechol peak was generally reduced during hypertension. We found that only in the C1 nucleus were the electrochemical peaks for catechols and indoles reciprocally related to blood pressure for both hypertension and hypotension. In preliminary experiments, we have also found that the catechol peak in the lateral hypothalamus is inversely and linearly related to serum osmolarity. In the renewal of this grant we will study catechol and indole metabolism in nucleus tractus solitarius, locus coeruleus, the C1 and A1 areas, the nucleus ambiguous, the paraventricular nucleus, the preoptic area and lateral hypothalamus during changes in serum osmolarity and circulating volume. In addition to in vivo electrochemistry, we will use in vivo dialysis to study norepinephrine and epinephrine release in C1 nucleus during drug induced changes in blood pressure. Effects of osmotic changes will be compared in Sprague Dawley and vasopressin deficient Brattleboro rats. The ability of vasopressin to reset baroreceptor gain and lower catechols in NTS will be compared with the effect of vasopressin infusions on catechol and indole release in other brainstem nuclei. These experiments should characterize the role of monoamines in individual brainstem nuclei in maintaining blood pressure, serum osmolarity, and circulating volume. Results of these studies already suggest a new therapy for hypertension. Serotonin agonists and alpha-2 agonists may make a potent antihypertensive combination.

已知血清素和儿茶酚胺在 血压的调节。 血清素激动剂、α-2 受体 激动剂和多巴胺激动剂均已被证明可以降低血压 在高血压动物中。 患有高血压的人通常 用可乐定和α-甲基多巴治疗，这两种药物 通过中枢刺激 alpha-2 降低血压 肾上腺素受体。 尽管这些药物取得了治疗成功， 对于单个脑干核团如何 期间使用去甲肾上腺素、肾上腺素、多巴胺和血清素 血压的变化。 凭借体内新技术 电化学，我们已经能够跟踪时间进程 儿茶酚和 5-HIAA 浓度在药物- 诱发高血压和低血压。 第一次获奖期间 在此资助期间，我们发现血清素代谢物 5- 当血压升高时，大多数细胞核中的 HIAA 都会增加 增加。 儿茶酚峰通常在 高血压。 我们发现只有在C1核中 儿茶酚和吲哚的电化学峰相互对应 高血压和低血压都与血压有关。 在初步实验中，我们还发现儿茶酚 下丘脑外侧的峰值呈反比和线性相关 至血清渗透压。 在更新这笔赠款时，我们将研究 孤束核中的儿茶酚和吲哚代谢，位点 蓝斑、C1 和 A1 区、模糊核、 室旁核、视前区和外侧区 血清渗透压和循环变化期间下丘脑 体积。 除了体内电化学之外，我们还将使用 体内透析研究 C1 中去甲肾上腺素和肾上腺素的释放 药物引起血压变化期间的核。 的影响 将比较 Sprague Dawley 和 加压素缺乏的布拉特尔伯勒大鼠。 加压素的能力 重置压力感受器增益并降低 NTS 中的儿茶酚含量 与输注加压素对儿茶酚和 其他脑干核团中的吲哚释放。 这些实验 应描述单胺在个体中的作用 脑干核维持血压、血清渗透压、 和循环量。 这些研究的结果已经表明 高血压的新疗法。 血清素激动剂和 alpha-2 激动剂可以形成有效的抗高血压组合。