Роль нейрональной NO-синтазы в реализации респираторных эффектов провоспалительного цитокина ФНО-α

Abstract

In our previous studies we showed that an increase in the systemic or cerebral level of proinflammatory cytokines has a modulating effect on the reflex control of respiration. The aim of this study was to investigate the possible involvement of neuronal nitric oxide synthase (nNOS) in the hypoxic ventilatory response induced by an increased systemic level of the proinflammatory cytokine Tumor necrosis factor — α (TNF-α). To achieve this goal, we conducted experiments on urethane anesthetized rats with intravenous administration of TNF-α before and after pretreatment with 7-nitroindazole specific inhibitor of nNOS. The hypoxic ventilation response was assessed by rebreathing with a hypoxic gas mixture before and after administration of TNF-α. We found that TNF-α increased the lung ventilation in normoxia but decreased the ventilatory response to hypoxia. Pretreatment with nNOS inhibitor reduced respiratory effects of TNF-α. We believe that TNF-α can participate in the modulation of peripheral hypoxic chemoreflex not only in pathological, but also in normal physiological conditions through the activation of constitutive nNOS in the glomus cells of the carotid bodies. This makes the respiratory system urgently respond to an increase in the level of pro-inflammatory cytokines in the circulatory system. The obtained data made it possible to improve the understanding of how systemic inflammation affects the respiratory function.