ROLE OF NEUROPEPTIDES AND BIOGENIC AMINES IN STRESS AND BRAIN ISCHEMIA

神经肽和生物胺在压力和脑缺血中的作用

• 批准号: 6290596
• 负责人: JUAN M SAAVEDRA
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290596
• 关键词: angiotensin II; angiotensins; brain mapping; cerebellar cortex; estrogens; gender difference; gerbil /jird; hippocampus; hormone receptor; hormone regulation /control mechanism; human tissue; hyperprolactinemia; laboratory mouse; molecular cloning; neural plasticity; neuropeptide receptor; olivary body; progesterone; receptor expression; species difference

We have demonstrated that Angiotensin II, through stimulation of AT1 receptors, contributes to regulate cerebral blood flow and participates in the control of the central and peripheral reactions to stress. Peripheral administration of AT1 antagonists blocks not only peripheral but also brain AT1 receptors. We have found that previous administration of Angiotensin II AT1 receptor antagonists decreases brain edema and stroke volume by 50% in genetically hypertensive rats after temporal occlusion of the middle cerebral artery with reperfusion. In rats submitted to acute isolation stress, similar administration of AT1 antagonists significantly decreases adrenaline, noradrenaline, vasopressin and ACTH release, evidence of an inhibition of the sympathoadrenal and pituitary response to stress. These results indicate that administration of AT1 antagonists could be therapeutically useful for the prevention and treatment of brain ischemia and stress-related disorders. When comparable doses are used, AT1 antagonists are more effective in reducing brain ischemia than ACE inhibitors or calcium channel blockers. In addition, AT1 antagonists produce a modest, but consistent and significant, reduction in weight gain, when administered prior either to stress or brain ischemia. This indicates that the AT1 antagonists have multiple sites of action and sympatholytic effects with therapeutic potential in stress and brain ischemia - Brain. Stress. Cerebrovascular flow. Rats. gerbils. mice. Stroke. In situ hybridization. Cloning.

我们已经证明，血管紧张素II，通过刺激AT 1受体，有助于调节脑血流量，并参与控制的中枢和外周反应的压力。AT 1拮抗剂的外周给药不仅阻断外周而且阻断脑AT 1受体。我们已经发现，血管紧张素II AT 1受体拮抗剂的先前管理减少脑水肿和每搏输出量的50%，在遗传性高血压大鼠颞闭塞大脑中动脉再灌注后。在大鼠提交的急性隔离应激，类似的行政AT 1拮抗剂显着降低肾上腺素，去甲肾上腺素，血管加压素和ACTH的释放，抑制交感神经和垂体应激反应的证据。这些结果表明，AT 1拮抗剂的管理可能是治疗有用的预防和治疗脑缺血和应激相关的疾病。当使用相当的剂量时，AT 1拮抗剂在减少脑缺血方面比ACE抑制剂或钙通道阻滞剂更有效。此外，当在应激或脑缺血之前给药时，AT 1拮抗剂产生适度但一致且显著的体重增加减少。这表明AT 1拮抗剂具有多个作用位点和交感神经阻滞作用，在应激和脑缺血-脑中具有治疗潜力。应力脑血管流量大鼠沙鼠小鼠中风原位杂交克隆。