Hahn S M, Sullivan F J, DeLuca A M, Bacher J D, Liebmann J, Krishna M C, Coffin D, Mitchell J B
Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, USA.
Free Radic Biol Med. 1999 Sep;27(5-6):529-35. doi: 10.1016/s0891-5849(99)00099-4.
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.
活性氧在许多生理和病理过程中发挥着关键作用。氮氧化物是具有超氧化物歧化酶（SOD）模拟活性的稳定自由基化合物，已被证明在体外和体内均能抵御活性氧的毒性。Tempol是一种可穿透细胞的亲水性氮氧化物，可抵御氧化应激，也是一种体外和体内辐射防护剂。在评估氮氧化物的药理学和毒性过程中，将不同浓度的Tempol和另一种氮氧化物3-氨基甲酰基-PROXYL（3-CP）静脉注射给小型猪。Tempol引起与剂量相关的低血压，并伴有反射性心动过速和皮肤温度升高。通过Swan Ganz导管插入术（SGC）进行的有创血流动力学监测证实了Tempol的强效血管舒张作用。然而，3-CP对猪血压没有影响。在超氧化物歧化的不同催化速率常数的背景下讨论了Tempol和3-CP的血流动力学效应，这些常数可能影响全身一氧化氮（NO）水平并导致血管舒张。这些发现与超氧离子在血压调节中的作用一致，并且对氮氧化物的全身应用具有潜在意义。
