PACAP causes long‐term increases in sympathetic nerve activity and is necessary for the sympathetic response to acute intermittent hypoxia

Abstract

Overall objectiveTo determine if the sustained elevation of splanchnic sympathetic nerve activity (sSNA), termed long‐term facilitation (LTF), following acute intermittent hypoxia (AIH) is due to intermittent, release of sympathoexcitatory peptides, such as pituitary adenylate cyclase activating polypeptide (PACAP).MethodsIn urethane‐anaesthetized, artificially ventilated, male rats (n=18 Sprague–Dawley), we investigated the effect of 10, 45s, episodes of 10%O2–90%N2 every 5 min (AIH) on sSNA after intrathecal infusion of 10μl of vehicle, PACAP (300μM) or the PAC1/VPAC2 receptor antagonist, PACAP(6–38) (1mM). In a separate group of rats (n=6) without AIH, 10 doses of PACAP (10μL of 10μM) were given intrathecally every 5 min.ResultsVehicle‐treated rats showed a 31.0±8.1% increase in sSNA 60min after AIH, which doubled to 67.7±14.1% in PACAP treated rats. Infusing the PACAP antagonist PACAP(6–38) prior to AIH abolished sympathetic LTF (0.1±2.7%). The responses were significantly different (P<0.0001; 2‐way ANOVA). Intermittent, sub‐threshold, infusion of PACAP (10×10μM) was as effective as AIH in causing LTF (sSNA increase of 38.±8.0%).ConclusionPACAP, acting via spinal PAC1/VPAC2 receptors, is sufficient to cause sympathetic LTF in the absence of AIH and necessary for the elaboration of sympathetic LTF following AIH. Support provided by Macquarie University, ARC and NHMRC.