HCRT and hypertensive disorder: Exposing rats to higher concentrations of hypercarbic gas (e.g., 20% CO2) depolarizes OX neurons by interacting with pH/ CO2 chemosensitive K+ channels (Williams et al., 2007), and also causes subsequent release of orexin at post-synaptic targets in the brain and spinal cord to mobilize anxiety-like behavior, hypertension, and increases ventilatory responses (Johnson et al., 2012c, 2015).