Published online before print January 3, 2002, doi: 10.1161/hh0202.104530
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 25, 2001
Revised on November 30, 2001
Accepted on December 20, 2001
Carbon Monoxide--Releasing Molecules. Characterization of Biochemical and Vascular Activities
From the Vascular Biology Unit (R.M., J.E.C., R.F., P.S., C.J.G.), Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex, UK; and the Department of Chemistry (B.E.M.), University of Sheffield, Sheffield, UK.
* To whom correspondence should be addressed. E-mail: r.motterlini{at}ic.ac.uk.
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.
Key words: carbon monoxide • transitions metal carbonyls • heme oxygenase-1 • vascular function • gene expression
This article has been cited by other articles:
 |
|
 |
|
  J. Deshane, S. Chen, S. Caballero, A. Grochot-Przeczek, H. Was, S. Li Calzi, R. Lach, T. D. Hock, B. Chen, N. Hill-Kapturczak, et al. Stromal cell-derived factor 1 promotes angiogenesis via a heme oxygenase 1-dependent mechanism J. Exp. Med., March 19, 2007; 204(3): 605 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hill-Kapturczak and A. Agarwal Carbon monoxide: from silent killer to potential remedy Am J Physiol Renal Physiol, April 1, 2006; 290(4): F787 - F788. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Taille, J. El-Benna, S. Lanone, J. Boczkowski, and R. Motterlini Mitochondrial Respiratory Chain and NAD(P)H Oxidase Are Targets for the Antiproliferative Effect of Carbon Monoxide in Human Airway Smooth Muscle J. Biol. Chem., July 8, 2005; 280(27): 25350 - 25360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-S. Lee, H.-L. Tsai, and L.-Y. Chau Induction of Heme Oxygenase-1 Expression in Murine Macrophages Is Essential for the Anti-inflammatory Effect of Low Dose 15-Deoxy-{Delta}12,14-prostaglandin J2 J. Biol. Chem., May 23, 2003; 278(21): 19325 - 19330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Morse and A. M. K. Choi Heme Oxygenase-1 . The "Emerging Molecule" Has Arrived Am. J. Respir. Cell Mol. Biol., July 1, 2002; 27(1): 8 - 16. [Abstract] [Full Text] [PDF]
|
|