Superoxide dismutase mimetic modulates hyperoxic augmentation of the diaphragmatic response to poikilocapnic hypoxia in non-vagotomized rats.

A period of oxygen breathing enhances the subsequent respiratory responses to episodic hypoxia. Since hyperoxia increases a formation of reactive oxygen species (ROS) in lungs, in the present study we asked a question of whether superoxide anion produced during O(2) breathing would participate in the mechanisms of posthyperoxic enhancement of the response to hypoxia and whether afferent information from the lungs would contribute to this response. To scavenge a superoxide we used Tempol (4-hydroxy-2,2,6,6-tetra-methyl piperidine-N-oxyl), a superoxide dismutase mimetic. The respiratory activity of anesthetized, spontaneously breathing rats was assessed from the integrated costal diaphragm EMG. The experiments consisted of 3 min hypoxia (11% O(2)), before and after a 15 min period of breathing with 100% oxygen, with and without Tempol (33 mg/kg) preatreatment. The same protocol was performed in non-vagotomized and vagotomized rats. The results show that a SOD mimetic abolished both hyperoxia-induced slowing of respiration and posthyperoxic respiratory augmentation of the hypoxic response. The abolishment is due likely to a remodeling of the respiratory pattern involving lung vagal reeptors, since in vagotomized animals, the effects of Tempol were marginal.