Normobaric hyperoxia stimulates superoxide and nitric oxide production in the caudal solitary complex of rat brain slices

Abstract

Central CO-chemosensitive neurons in the caudal solitary complex (cSC) are stimulated not only by hypercapnic acidosis, but by hyperoxia as well. While a cellular mechanism for the CO response has yet to be isolated, previous data show that a redox-sensitive mechanism underlies neuronal excitability to hyperoxia. However, it remains unknown how changes in Po affect the production of reactive oxygen and nitrogen species (RONS) in the cSC that can lead to increased cellular excitability and, with larger doses, to cellular dysfunction and death. To this end, we used fluorescence microscopy in real time to determine how normobaric hyperoxia increases the production of key RONS in the cSC. Because neurons in the region are CO sensitive, we also examined the potential effects of CO narcosis, used during euthanasia before brain slice harvesting, on RONS production. Our findings show that normobaric hyperoxia (0.4 → 0.95 atmospheres absolute O) increases the fluorescence rates of fluorogenic dyes specific to both superoxide and nitric oxide. Interestingly, different results were seen for superoxide fluorescence when CO narcosis was used during euthanasia, suggesting long-lasting changes in superoxide production and/or antioxidant activity subsequent to CO narcosis before brain slicing. Further research needs to distinguish whether the increased levels of RONS reported here are merely increases in oxidative and nitrosative signaling or, alternatively, evidence of redox and nitrosative stress.

Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats

“…RVSP decreased in the Sham and PPVL groups during ventilation with hyperoxic gas. However, RVSP increased markedly in the CBDL+PPVL group with no change in the CBDL group during ventilation with hyperoxic gas, which may be related to reducing the bioavailability of NO by oxygen [52]. mBP in the CBDL+PPVL and CBDL groups was lower than that in the Sham group.…”

“…Hyperoxic gas recovered the arterial pressure because of direct effect of oxygen on increasing the vascular resistance and reducing the bioavailability of NO. [52,59] The heart rate decreased a little (data not shown) at the beginning of hypoxic maneuver linked to a reduction in depolarization rate of cardiac pacemaker cells [65]. It was followed by a tachycardia induced by both sympathetic activity and vagal withdrawal subsequent to the chemo-reflex activity [57].…”

Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats

“…RVSP decreased in the Sham and PPVL groups during ventilation with hyperoxic gas. However, RVSP increased markedly in the CBDL+PPVL group with no change in the CBDL group during ventilation with hyperoxic gas, which may be related to reducing the bioavailability of NO by oxygen [53].…”

“…It should be noted that alterations of mBP in the CBDL and CBDL+PPVL groups were small during ventilation with hypoxic gas which may be linked to the increase of heart rate and volume overload in cirrhotic animals. Hyperoxic gas recovered the arterial pressure because of direct effect of oxygen on increasing the vascular resistance and reducing the bioavailability of NO [53,60].…”

Is an increased PaO2 in a normobaric state safe in acute CO poisoning?

“…Hyperoxia‐induced hyperventilation results in some degree of hypocapnia, which is associated with a reduction in the coronary and cerebral blood flows. Apart from the potential for hypocapnia, there is also free radical generation, resulting in neuronal injury and death via cellular metabolic failure and apoptosis, which can aggravate cerebral injury . Early hyperoxia exposure was independently associated with poor neurological function at hospital discharge or mortality in post‐cardiac arrest patients and patients with traumatic brain injury and sepsis .…”