Figure 4.

Spinal inhibition of p38 MAPK restored AIH-induced pLTF after IH-1, but did not alter the hypoxic responses or pLTF in normoxic controls. A–C, Representative integrated phrenic neurograms during AIH protocols for rats receiving normoxia + p38 MAPK inhibitor (SB202190, 1 mm, intrathecal; A), IH-1 + p38 MAPK inhibitor (B), and time control + p38 MAPK inhibitor (no AIH, C). Development of pLTF is evident as a progressive increase in phrenic nerve amplitude from baseline (black dashed line) over 90 min in normoxic + p38 MAPK inhibitor and IH-1 + p38 MAPK inhibitor rats, but not in time control + p38 MAPK inhibitor rats. D, Inhibition of p38 MAPK did not alter short-term hypoxic responses between Nx + veh (123 ± 17%), IH-1 + veh (100 ± 19%), Nx + p38 inhib (100 ± 17%), and IH-1 + p38 inhib (108 ± 7%) rats (one-way ANOVA). E, After p38 inhibitor, there was no difference between rats treated with IH-1 or normoxia. Ninety minutes after AIH, pLTF was evident in Nx + vehicle (57 ± 19%), Nx + p38 inhibitor (73 ± 15%), and IH-1 + p38 inhibitor (58 ± 2%), but pLTF in IH-1 + vehicle (11 ± 14%) rats was significantly reduced compared to the aforementioned groups and was not different from time controls + vehicle (13 ± 11%) or time controls + p38 inhibitor (−7 ± 13%). *p < 0.05, **p < 0.01, ***p < 0.001 (significantly different from time control + vehicle); ^###p < 0.001 (significantly different from time control + p38 inhibitor); ^@p < 0.05, ^@@p < 0.01, ^@@@p < 0.001 (significantly different from IH-1 + vehicle; two-way RM ANOVA, Fisher LSD post-test).