title: Hemodynamic effect of the nitroxide superoxide dismutase mimics.
abstract: Reactive oxygen species play critical roles in a number of physiologic and pathologic processes. Nitroxides are stable free radical compounds that possess superoxide dismutase (SOD) mimetic activity and have been shown to protect against the toxicity of reactive oxygen species in vitro and in vivo. Tempol, a cell-permeable hydrophilic nitroxide, protects against oxidative stress and also is an in vitro and in vivo radioprotector. In the course of evaluating the pharmacology and toxicity of the nitroxides, Tempol and another nitroxide, 3-carbamoyl-PROXYL (3-CP), were administered intravenously in various concentrations to miniature swine. Tempol caused dose-related hypotension accompanied by reflex tachycardia and increased skin temperature. Invasive hemodynamic monitoring with Swan Ganz catheterization (SGC) confirmed the potent vasodilative effect of Tempol. However, 3-CP had no effect on porcine blood pressure. The hemodynamic effects of Tempol and 3-CP are discussed in the context of differential catalytic rate constants for superoxide disumation that may impact systemic nitric oxide (NO) levels and lead to vasodilation. These findings are consistent with a role for the superoxide ion in the modulation of blood pressure and have potential implications for the systemic use of nitroxides.
authors.affiliation: Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Hahn
authors.forename: F J
authors.initials: FJ
authors.lastname: Sullivan
authors.forename: A M
authors.initials: AM
authors.lastname: DeLuca
authors.forename: J D
authors.initials: JD
authors.lastname: Bacher
authors.forename: J
authors.initials: J
authors.lastname: Liebmann
authors.forename: M C
authors.initials: MC
authors.lastname: Krishna
authors.forename: D
authors.initials: D
authors.lastname: Coffin
authors.forename: J B
authors.initials: JB
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D009569:Nitric Oxide / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012881:Skin Temperature / Q000187:drug effects; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature; D013610:Tachycardia / Q000139:chemically induced; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D003497:Cyclic N-Oxides; D011759:Pyrrolidines; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D013113:Spin Labels; D014665:Vasodilator Agents; D009569:Nitric Oxide; C077426:3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl; D013482:Superoxide Dismutase; C001803:tempol