NEUROCHEMICAL STUDIES OF CNS CARDIOVASCULAR CENTERS

中枢神经系统心血管中心的神经化学研究

• 批准号: 3347394
• 负责人: ANDREJ ROTTER
• 金额: $ 10.06万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3347394
• 关键词: antihypertensive agents; autoradiography; cardiovascular system; central nervous system; dorsal motor nucleus; gamma aminobutyrate; glutamates; histochemistry /cytochemistry; hypertension; ligands; medulla oblongata; microscopy; monoclonal antibody; neural information processing; neural transmission; neurochemistry; neurotransmitters; serotonin; solitary tract nucleus; spinal cord; vasomotion

There are several drugs currently used to treat hypertension which appear to act on the cardiovascular control centers of the central nervous system. Such drugs include clonidine and Alpha-methyldopa, both of which are Alpha2-adrenergic receptor agonists. Other CNS receptors may also be involved in hypertensive states and their identity might lead to the development of new anti-hypertensive drugs. We wish to study the distribution of five neurotransmitter and their corresponding receptors in central nervous system cardiovascular control centers (for example, the nucleus ambiguus, nucleus of the Xth nerve, nucleus of the solitary tract and the intermediolateral column of the spinal cord), in order to determine which drugs may potentially act at these sites. Markers for adrenergic, cholinergic, gamma-aminobutyric acid, glutamate, and serotonin transmission and their receptors will be detected by light microscope histochemistry and autoradiography. Receptor concentrations of cardiac and vasomotor control centers in adult rats will also be determined after deafferentation and axotomy. The changes observed will indicate whether the receptors tested are localized pre- or postsynaptically. In addition, the concentration of neurotransmitter and drug receptors in the cardiovascular control centers of neonatal and adult normotensive and spontaneously hypertensive rats will be compared. This comparison might reveal the chemical nature of central transmitter system malfunction underlying hypertension.

目前有多种治疗高血压的药物 作用于中枢神经的心血管控制中心 系统。 此类药物包括可乐定和α-甲基多巴，这两种药物 是α2-肾上腺素能受体激动剂。 其他中枢神经系统受体也可能是 参与高血压状态及其身份可能会导致 新型抗高血压药物的开发。 我们希望研究 五种神经递质及其相应受体的分布 中枢神经系统心血管控制中心（例如， 疑核、X 神经核、孤束核 和脊髓的中间外侧柱），以确定 哪些药物可能在这些部位发挥作用。 肾上腺素能标记物， 胆碱能、γ-氨基丁酸、谷氨酸和血清素传输 其受体将通过光学显微镜组织化学检测 放射自显影。 心脏和血管舒缩控制的受体浓度 成年大鼠的中心也将在传入神经阻滞和 轴切术。 观察到的变化将表明受体是否受到测试 定位于突触前或突触后。 此外，浓度 心血管控制中心的神经递质和药物受体 新生和成年正常血压和自发性高血压大鼠的 进行比较。 这种比较可能揭示中心的化学性质 高血压的传导系统故障。