Role of CO in Cerebrovascular EDHF-mediated Dilation

CO 在 EDHF 介导的脑血管扩张中的作用

• 批准号: 7119598
• 负责人: JON J ANDRESEN
• 金额: $ 4.88万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-06 至 2007-09-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7119598
• 关键词: carbon monoxide; cerebral artery; cerebrovascular system; heme oxygenase; immunocytochemistry; laboratory rat; nitric oxide; postdoctoral investigator; vascular endothelium; vasodilation; vasodilators; western blottings

DESCRIPTION (provided by applicant): Carbon monoxide (CO) is endogenously produced by heme oxygenase (HO) and CO may be an important signaling molecule in the vasculature including cerebral vessels. Endothelium-derived hyperpolarization factor (EDHF) relaxes blood vessels and may predominate over nitric oxide (NO) in resistance sized vessels. EDHF may also help to preserve vascular function in disease conditions where NO is reduced. This proposal will examine the role of CO in EDHF-mediated dilation in cerebral arteries. My preliminary data demonstrate that inhibition of HO with Cr(lll) mesoporphyrin IX (CrMP) blocks EDHF-mediated dilation to DTP in the rat middle cerebral artery (MCA). In the rat MCA, CO itself is not a dilator, however, in the presence of CrMP, exogenous CO restores EDHF-mediated dilation. These data suggest that CO plays a permissive-like role in EDHF-mediated dilation. This proposal will examine conditions in which CO is important for vasodilation in the rat MCA and will begin to examine the mechanism by which CO influences EDHF-mediated dilation in the rat MCA. Thus, this proposal brings together, for the first time, two important fields of study, CO and EDHF.

描述（申请人提供）：一氧化碳（CO）由血红素加氧酶（HO）内源性产生，CO可能是包括脑血管在内的脉管系统中的重要信号分子。内皮源性超极化因子 (EDHF) 可以放松血管，并且在阻力大小的血管中可能比一氧化氮 (NO) 更占优势。 EDHF 还可能有助于在 NO 减少的疾病条件下保持血管功能。该提案将研究 CO 在 EDHF 介导的脑动脉扩张中的作用。我的初步数据表明，用 Cr(III) 中卟啉 IX (CrMP) 抑制 H2O2 可阻断 EDHF 介导的大鼠大脑中动脉 (MCA) 中 DTP 的扩张。在大鼠 MCA 中，CO 本身不是扩张剂，然而，在 CrMP 存在的情况下，外源 CO 可以恢复 EDHF 介导的扩张。这些数据表明，CO 在 EDHF 介导的扩张中发挥着类似许可的作用。该提案将研究 CO 对于大鼠 MCA 血管舒张至关重要的条件，并将开始研究 CO 影响大鼠 MCA 中 EDHF 介导的扩张的机制。因此，该提案首次汇集了两个重要的研究领域：CO 和 EDHF。