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: 3341776
• 负责人: CURT R FREED
• 金额: $ 9.8万
• 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/3341776
• 关键词: alpha adrenergic receptor; antihypertensive agents; cardiovascular disorder chemotherapy; cardiovascular pharmacology; catecholamines; clonidine; dopamine; electrochemistry; epinephrine; hormone metabolism; hormone regulation /control mechanism; human therapy evaluation; hypotension; laboratory rat; 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免疫系统中起作用。 调节血压。 5-羟色胺激动剂，α-2受体 激动剂和多巴胺激动剂都被证明可以降低血液中 在高血压动物中。 高血压患者通常 用可乐定和阿尔法甲基多巴治疗，这两种药物 通过中枢刺激α-2降低血压 肾上腺素受体。 尽管这些药物在治疗上取得了成功， 目前还没有关于脑干细胞核 使用去甲肾上腺素，肾上腺素，多巴胺和血清素， 血压的变化。 利用新的活体技术 电化学，我们已经能够遵循的时间过程， 儿茶酚和5-HIAA浓度连续用药期间， 诱发高血压和低血压。 第一次颁奖时 在此期间，我们发现血清素代谢物5- 当血压升高时，大多数核团的HIAA增加。 增加 儿茶酚峰在过程中通常降低， 高血压 我们发现，只有在C1核中， 儿茶酚和吲哚的电化学峰 与高血压和低血压的血压相关。 在初步实验中，我们还发现， 外侧下丘脑的峰值呈负线性相关 血清渗透压。 在更新这项补助金时，我们将研究 孤束核的儿茶酚和吲哚代谢 蓝斑、C1和A1区、疑核、 室旁核、视前区和外侧核 下丘脑在血清渗透压和循环的变化 音量. 除了体内电化学，我们还将在 体内透析以研究C1中的去甲肾上腺素和肾上腺素释放 核在药物引起的血压变化。 的影响 将比较Sprague道利和 加压素缺乏的布拉特波罗大鼠。 加压素的能力 重置压力感受器增益和降低NTS中的儿茶酚， 与加压素输注对儿茶酚和 其他脑干核团吲哚释放。 这些实验 应表征单胺在个体中的作用 脑干核团在维持血压，血清渗透压， 和循环量。 这些研究的结果已经表明， 治疗高血压的新方法 5-羟色胺激动剂和α 2 激动剂可以制成有效的抗高血压组合。