S-Nitroso-l-cysteine and ventilatory drive: A pediatric perspective.

Though endogenous S-nitroso-l-cysteine (l-CSNO) signaling at the level of the carotid body increases minute ventilation (v̇E ), neither the background data nor the potential clinical relevance are well-understood by pulmonologists in general, or by pediatric pulmonologists in particular. Here, we first review how regulation of the synthesis, activation, transmembrane transport, target interaction, and degradation of l-CSNO can affect the ventilatory drive. In particular, we review l-CSNO formation by hemoglobin R to T conformational change and by nitric oxide (NO) synthases (NOS), and the downstream effects on v̇E through interaction with voltage-gated K+ (Kv) channel proteins and other targets in the peripheral and central nervous systems. We will review how these effects are independent of-and, in fact may be opposite to-those of NO. Next, we will review evidence that specific elements of this pathway may underlie disorders of respiratory control in childhood. Finally, we will review the potential clinical implications of this pathway in the development of respiratory stimulants, with a particular focus on potential pediatric applications.