Carbon monoxide (CO) is generated in living organisms during the degradation of heme by the enzyme heme oxygenase, which exists in constitutive (HO-2 and HO-3) and inducible (HO-1) isoforms. Carbon monoxide gas is known to dilate blood vessels in a manner similar to nitric oxide and has been recently shown to possess antiinflammatory and antiapoptotic properties. We report that a series of transition metal carbonyls, termed here carbon monoxide-releasing molecules (CO-RMs), liberate CO to elicit direct biological activities. Specifically, spectrophotometric and NMR analysis revealed that dimanganese decacarbonyl and tricarbonyldichlororuthenium (II) dimer release CO in a concentration-dependent manner. Moreover, CO-RMs caused sustained vasodilation in precontracted rat aortic rings, attenuated coronary vasoconstriction in hearts ex vivo, and significantly reduced acute hypertension in vivo. These vascular effects were mimicked by induction of HO-1 after treatment of animals with hemin, which increases endogenously generated CO. Thus, we have identified a novel class of compounds that are useful as prototypes for studying the bioactivity of CO. In the long term, transition metal carbonyls could be utilized for the therapeutic delivery of CO to alleviate vascular- and immuno-related dysfunctions. The full text of this article is available at http://www.circresaha.org.

中文翻译：

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一氧化碳释放分子：生化和血管活性的表征。

一氧化碳（CO）是在血红素氧合酶降解血红素的过程中在生物体内产生的，该酶以组成型（HO-2和HO-3）和可诱导型（HO-1）亚型存在。一氧化碳气体以类似于一氧化氮的方式扩张血管，并且最近已显示具有抗炎和抗凋亡特性。我们报告了一系列过渡金属羰基，在这里称为一氧化碳释放分子（CO-RMs），释放出CO来引发直接的生物活性。具体而言，分光光度法和NMR分析表明，十羰基二锰和三羰基二氯钌（II）二聚体以浓度依赖的方式释放CO。此外，CO-RMs会导致预收缩大鼠主动脉环中持续的血管舒张，离体心脏的冠状血管收缩变弱，并显着降低了体内的急性高血压。通过用血红素处理动物后诱导HO-1可以模仿这些血管效应，从而增加内源性产生的CO。因此，我们已经鉴定出了一类新型化合物，可用作研究CO的生物活性的原型。 ，过渡金属羰基化合物可用于治疗性释放CO，以减轻与血管和免疫相关的功能障碍。本文的全文可从http://www.circresaha.org获得。过渡金属羰基化合物可用于治疗性释放CO，以减轻与血管和免疫有关的功能障碍。本文的全文可从http://www.circresaha.org获得。过渡金属羰基化合物可用于治疗性释放CO，以减轻与血管和免疫有关的功能障碍。本文的全文可从http://www.circresaha.org获得。