title: Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions.
abstract: Carbon monoxide (CO) is a pollutant commonly recognized for its toxicological attributes, including CNS and cardiovascular effects. But CO is also formed endogenously in mammalian tissues. Endogenously formed CO normally arises from heme degradation in a reaction catalyzed by heme oxygenase. While inhibitors of endogenous CO production can raise arterial pressure, heme loading can enhance CO production and lead to vasodepression. Both central and peripheral tissues possess heme oxygenases and generate CO from heme, but the inability of heme substrate to cross the blood brain barrier suggests the CNS heme-heme oxygenase-CO system may be independent of the periphery. In the CNS, CO apparently acts in the nucleus tractus solitarii (NTS) promoting changes in glutamatergic neurotransmission and lowering blood pressure. At the periphery, the heme-heme oxygenase-CO system can affect cardiovascular functions in a two-fold manner; specifically: 1) heme-derived CO generated within vascular smooth muscle (VSM) can promote vasodilation, but 2) its actions on the endothelium apparently can promote vasoconstriction. Thus, it seems reasonable that the CNS-, VSM- and endothelial-dependent actions of the heme-heme oxygenase-CO system may all affect cardiac output and vascular resistance, and subsequently blood pressure.
authors.affiliation: Departamento de Fisiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brasil.
authors.forename: R A
authors.initials: RA
authors.lastname: Johnson
authors.forename: F
authors.initials: F
authors.lastname: Kozma
authors.forename: E
authors.initials: E
authors.lastname: Colombari
mesh_terms: D001794:Blood Pressure / Q000502:physiology; D002248:Carbon Monoxide / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D006418:Heme / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D017552:Solitary Nucleus / Q000502:physiology*; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D006418:Heme; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)