Ингибирование гиперпродукции оксида азота в условиях прогрессивно нарастающей гипоксии на фоне действия ИЛ-1β снижает выживаемость крыс после острой гипоксии

Abstract

The role of the nitric oxide (NO) in the compensatory reactions the organism to increasing acute normobaric hypoxia was evaluated in anesthetized Wistar rats with an increased proinflammatory cytokine interleukin-1beta (IL-1β) levels. A progressively increasing hypoxia from normoxia up to apnea was created using an experimental “rebreathing” model. We found that the blockade of NO by the non-selective inhibitor of NO-synthase L-NAME inhibits the compensatory increase of lung ventilation in response to the increasing hypoxic hypoxia to a greater extent than with a discrete increase of the IL-1β, which could be a consequence of the decreased activity of the peripheral chemoreception. The observed blood pressure drop under the IL-1β administration at normoxic conditions, and its increase to control values when NO was inhibited, were accompanied with the changes in external respiration and arterial blood oxygenation, indicating the role of NO in the formation of integrative respiratory and cardiovascular reactions under pathological and extreme conditions. In rats under NO blockade, the saturation levels during the acute hypoxia did not decrease, but exceeded both control values, and those observed under the action of IL-1β. Such reaction could be the result of hypoxic hypometabolism (a decrease of the metabolic rate), which is characterized by the decrease of the oxygen consumption as a result of a sharp arterial blood O2 drop. We also found that the NO inhibition under progressively increasing hypoxia under the action of IL-1β inhibits the spontaneous recovery of inspiratory activity after apnea, and decreases the survival rate in the post-hypoxic period. Thus, the analysis of the results indicates the involvement of nitric oxide in the mechanisms of proinflammatory cytokine interleukin-1 beta effects on the tolerance to the increasing acute normobaric hypoxia in rats.