Role of Carbon Monoxide in Blood Pressure Regulation

Abstract

Carbon monoxide (CO) is an odorless, colorless, tasteless gas that is generated in the environment as the result of combustion from stoves and engines among other sources. Approximately 500 people per year in the United States are victims of nonfire-associated CO poisoning according to the Centers for Disease Control and Prevention. CO poisoning is often fatal because of its interaction with hemoglobin, which renders it incapable of carrying oxygen-causing organs to become severely hypoxic. CO inhalation is believed to be fatally toxic at concentrations as little as 800 parts per million (ppm) or 0.08% in the air. Despite the lethal nature of this gas, several recent studies suggest that CO inhalation at low doses (≤250 ppm), as well as increases in CO levels using CO releasing molecules (CORMs), offers protection against ischemic injury in the heart, liver, and kidney.1–4 CO is endogenously produced in the body as a result of the metabolism of heme by heme oxygenase (HO), as well as from lipid peroxidation.5,6 The catabolism of heme by HO also produces an equimolar amount of biliverdin, which is rapidly converted in the cell to bilirubin by the enzyme biliverdin reductase.7 There are 2 major isoforms of HO responsible for CO production. HO-1 is expressed at very low levels under normal conditions but is highly induced by several stimuli, including heavy metals, ultraviolet light, endotoxin, shear stress, hypoxia, and oxidants.8 HO-2 is the constitutively expressed form of the enzyme with the highest levels observed in the brain and testes.9 Experimental evidence has demonstrated that systemic induction of HO has several beneficial actions on the cardiovascular system, including lowering of blood pressure, protection against myocardial infarction, and prevention of atherosclerosis.10–12 Although the cardiovascular actions of HO induction have been established, the role of CO in …