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: 3341772
• 负责人: CURT R FREED
• 金额: $ 7.29万
• 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 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341772
• 关键词: 5 hydroxytryptophan; antihypertensive agents; blood pressure; catecholamines; centrally acting drug; clonidine; dorsal raphe nucleus; electrochemistry; hormone regulation /control mechanism; hydralazine; hypotension; neural information processing; neurotransmitters; phenylephrine; propranolol; serotonin; sympathetic nervous system; vasodilators

Brain catecholamines and serotonin have been shown to be involved in central nervous system regulation of blood pressure. In particular, hypothalamic and brainstem nuclei containing high concentrations of these neurotransmitters form an axis of blood pressure regulatory neurons. Clinically important antihypertensive agents such as alphamethyldopa and clonidine reduce sympathetic outflow from the brain by inhibiting central catecholamine neurons. While noradrenergic neurons have been most implicated in the mechanism of action of central acting antihypertensive drugs, serotonergic neurons also play a role in blood pressure regulation. We have shown that chronic infusions of the serotonin precursor 5-hydroxytryptophan increase brain serotonin turnover and reduce blood pressure in normotensive rats. We have now adapted in vivo electrochemical techniques to make it possible to study nonrepinephrine and serotonin release continuously from specific nuclei in brain of awake rats. Preliminary experiments have shown that intravenous phenylephrine infusions which increase blood pressure cause an increase in Serotonin release in dorsal raphe nucleus. Norepinephrine release initially falls but then subsequently increases. These results are compatible with the hypothesis that the brain compensates for hypertension by reducing sympathetic outflow through increased central serotonergic tone and reduced noradrenergic tone. We plan to use in vivo electrochemistry to study noradrenergic and serotonergic neuronal responses to acute and chronic hypertension and hypotension. Awake rats from both normotensive and hypertensive strains will be studied. Hypertension will be produced with infusions of vasopressors such as phenylephrine and hypotension will be induced by vasodilators such as hydralazine and beta blockers such as propranolol. In addition, central acting antihypertensive drugs such as clonidine will be evaluated. Regions to be studied include hypothalamus, locus coeruleus, nucleus tractus solitarius and dorsal raphe nucleus. These experiments should help clarify the interactive role of norepinephrine and serotonin in blood pressure regulation and indicate the relative importance of each neurotransmitter in individual vasoregulatory nuclei.

大脑中的儿茶酚胺和血清素已经被证明与 中枢神经系统调节血压。 特别是， 下丘脑和脑干核含有高浓度的这些 神经递质形成血压调节神经元的轴。 临床上重要的抗高血压药物，如N-甲基多巴和 可乐定通过抑制中枢神经系统， 儿茶酚胺神经元 虽然去甲肾上腺素能神经元大多数 与中枢作用抗高血压药物的作用机制有关 药物，肾上腺素能神经元也在血压调节中发挥作用。 我们已经证明长期注射血清素前体 5-羟色氨酸增加脑血清素周转并减少血液 血压正常大鼠的血压。 我们现在已经调整了体内电化学 研究非肾上腺素和血清素的技术 从清醒大鼠脑内特定核团持续释放。 初步实验表明，静脉注射苯肾上腺素 这会增加血压，导致血清素释放增加， 中缝背核 去甲肾上腺素的释放最初福尔斯下降， 随后增加。 这些结果与假设相符 大脑通过减少交感神经流出来补偿高血压 通过增加中枢肾上腺素能紧张和减少去甲肾上腺素能紧张， 语气 我们计划使用体内电化学来研究去甲肾上腺素能和 急性和慢性高血压对肾上腺素能神经元的反应， 低血压 正常血压和高血压品系的清醒大鼠 将被研究。 高血压将产生与输液 血管加压药如苯肾上腺素和低血压将由 血管扩张剂如肼苯哒嗪和β受体阻滞剂如普萘洛尔。 在 此外，中枢作用的抗高血压药物，如可乐定， 评估。 待研究的区域包括下丘脑，蓝斑， 孤束核和中缝背核。 这些实验 应该有助于阐明去甲肾上腺素和血清素在 血压调节，并指出每一个的相对重要性 单个血管调节核的神经递质。