Role of CO in Cerebrovascular EDHF-mediated Dilation

描述(申请人提供)：一氧化碳(CO)是由血红素加氧酶(HO)内源性产生的，一氧化碳可能是包括脑血管在内的血管系统中的重要信号分子。血管内皮衍生超极化因子(EDHF)松弛血管，在阻力大小的血管中可能比一氧化氮(NO)占优势。EDHF还有助于在NO降低的疾病条件下保护血管功能。这项提议将研究一氧化碳在EDHF介导的脑动脉扩张中的作用。我的初步数据表明，在大鼠大脑中动脉(MCA)上，用铬(111)中卟啉IX(CRMP)抑制HO可阻断EDHF介导的DTP的扩张。在大鼠大脑中动脉，CO本身不是扩张剂，但在CRMP存在的情况下，外源性CO可恢复EDHF介导的扩张。这些数据表明，CO在EDHF介导的血管扩张中起着类似许可的作用。这项建议将研究一氧化碳对大鼠大脑中动脉血管扩张重要的条件，并将开始研究一氧化碳影响大鼠大脑中动脉EDHF介导的扩张的机制。因此，这项建议首次将CO和EDHF这两个重要的研究领域结合在一起。

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.