Pro-inflammatory cytokines do not affect basal or hypoxia-stimulated discharge of rat vagal paraganglia.

Vagal paraganglia are structurally similar to the carotid body and are chemosensitive to reduction in the P(O(2)). We hypothesized that they may also mediate communication between the immune system and the central nervous system via pro-inflammatory cytokines or endotoxin. In vitro experiments with isolated superior laryngeal nerve (SLN) paraganglia were performed to test this hypothesis. We exposed the cells to increasing concentrations of interleukin-1ß, tumour necrosis factor-α or interleukin-6 (0.1, 0.3 and 1 ng ml(-1)) or bacterial lipopolysaccharide (LPS, 10 and 100 ng ml(-1)) during both normoxia ( P(O(2)) ≈ 100 mmHg) and hypoxia (P(O(2)) < 40 mmHg) whilst single-fibre recordings were made from the main SLN trunk using a glass suction electrode. The results of these experiments confirmed previous findings that these cells respond strongly to changes in P(O(2)), significantly increasing their discharge rate in response to hypoxia (from 0.71 ± 0.23 to 10.95 ± 1.74 Hz, P < 0.0001). However, neither the cytokines nor LPS had any significant effect on the baseline discharge rate of the SLN units at any concentration. When compared with time-matched controls, the cytokines and LPS also had no effect on the peak hypoxic discharge rate of the SLN (P = 0.59 and 0.65, respectively). In conclusion, neither the basal nor the hypoxic discharge rate of the SLN paraganglia is modulated by the inflammatory mediators tested above, suggesting that these structures are not the afferent limb of an 'immune reflex'.

The effect of pro-inflammatory cytokines on the discharge rate of vagal nerve paraganglia in the rat.

Vagal paraganglia resemble the carotid body and are chemosensitive to reduction in the partial pressure of oxygen (P O2) (O'Leary et al., 2004). We hypothesised that they may also mediate communication between the immune system and the central nervous system and more specifically respond to the pro-inflammatory cytokines: interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha). We recorded axonal firing rate of isolated superfused rat glomus cells - located at the bifurcation of the superior laryngeal nerve - to IL-1 beta or TNF-alpha at concentrations of 0.5 ng/ml, 5 ng/ml and 50 ng/ml. Twenty-three successful single fibre recordings were obtained from 10 animals. IL-1 beta and TNF-alpha had no statistically significant effect on the frequency of action potentials observed (p=0.39 and 0.42, respectively, repeated measures ANOVA). The activity of both cytokines was tested by observing translocation of P65-NF kappaB from cytoplasm to nucleus in cultured HELA cells. In conclusion, an immune role for SLN paraganglia has not been established.

Superoxide scavengers improve rat pharyngeal dilator muscle performance.

Obstructive sleep apnea is a common disorder associated with upper airway muscle dysfunction. Agents that improve respiratory muscle performance may be useful as an adjunct therapy. The aim of this study was to examine the effects of antioxidants on rat pharyngeal dilator muscle performance. Adult male Wistar rats were killed humanely and isometric contractile properties of isolated sternohyoid muscle strips were examined in physiological salt solution at 35 degrees C in vitro. Muscle strips were incubated in tissue baths under hyperoxic (95%O(2)/5%CO(2)) or hypoxic (95%N(2)/5%CO(2)) conditions in the absence (control) or presence of the antioxidants: N-acetylcysteine (10 mM), Tiron (10 mM), or Tempol (10 mM). Force-frequency relationship was determined in response to supramaximal stimulation (10-100 Hz in increments of 10-20 Hz, train duration: 300 ms). Isometric force was also recorded during repetitive muscle stimulation (40 Hz, 300 ms every 2 s for 2 min). Under hyperoxic conditions, Tiron and Tempol, but not N-acetylcysteine, significantly increased sternohyoid muscle force and caused a left-shift in the force-frequency relationship. In addition, Tempol had a significant positive inotropic effect over the initial 90 seconds of repeated muscle activation. Hypoxia caused a significant decrease in sternohyoid muscle force. Under hypoxic conditions, Tempol-incubated muscles generated significantly higher forces compared with control muscles and showed improved performance in the early phase of the fatigue trial. This study illustrates that superoxide scavengers increase upper airway muscle force and that this effect persists under hypoxic conditions. We conclude that antioxidant treatment may be beneficial as a therapy in obstructive sleep apnea.