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The control of breathing has been a long examined enigma. Despite the critical biological significance of respiratory control, the framework of the molecular interactions which generate and regulate these incredible phenomena are only beginning to be delineated. Recent advances in the understanding the role of nitric oxide (NO) as a signaling molecule have facilitated our understanding of the high level complexities and multiple interacting pathways in many biological systems including those underlying neural control of ventilation. In this review, we will examine the current understanding of the contribution of NO and NO-related compounds to the neural control of breathing. We will focus our attention on the role played by NO in peripheral chemoreceptor control of ventilation and also explore the contribution of NO-mediated systems in central nervous system pathways underlying the control of ventilation. Additionally, the importance of NO and NO derivatives in synaptic plasticity and adaptive mechanisms to long-term perturbations during development will also be addressed.

Intermittent hypoxia (IH) induces alterations in respiratory control that reflect various types of ventilatory plasticity. In freely behaving rats, acute exposure to IH elicits enhancements in normoxic minute ventilation (VE), termed ventilatory long-term facilitation. Exposure to longer time periods of IH induces unique ventilatory adaptations to intermittent hypoxia (VAIH). We hypothesized that long-term IH-induced ventilatory plasticity may be developmentally regulated and thus, IH exposures at progressively later post-natal ages may elicit differential effects on the magnitude of VAIH. To examine this issue, male Sprague–Dawley rats were exposed to 30 continuous days of IH beginning at post-natal ages 1, 10, 30, 60, 180, 360, and 540 days. Control animals were exposed to normoxic conditions with room air. Normoxic VE was significantly higher in IH-exposed rats (p