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AT1受体，有助于调节脑血流，并参与控制中枢和外周对应激的反应。外周应用AT1拮抗剂不仅可以阻断外周AT1受体，还可以阻断大脑AT1受体。我们发现，在遗传性高血压大鼠大脑中动脉短暂闭塞再灌流后，先前给予血管紧张素II AT1受体拮抗剂可使脑水肿和每搏量减少50%。在接受急性隔离应激的大鼠中，给予类似的AT1拮抗剂显著减少肾上腺素、去甲肾上腺素、加压素和ACTH的释放，这是交感肾上腺和垂体对应激反应受到抑制的证据。这些结果表明，给予AT1拮抗剂可用于预防和治疗脑缺血和应激相关疾病。当使用相同剂量时，AT1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，AT1拮抗剂在应激或脑缺血之前给药时，体重增加的幅度不大，但持续且显著。这表明AT1拮抗剂在应激和脑缺血中具有多个作用部位和具有治疗潜力的交感神经作用。压力。脑血管血流。老鼠。沙鼠。老鼠。卒中。原位杂交。克隆。