Mechanisms reducing parasympathetic activity in chronic hypoxia

Abstract: Parasympathetic activity is reduced in chronic hypoxia, but the underlying mechanism(s) are unclear. We investigated whether (i) arterial chemoreflex activation, (ii) increased pulmonary ventilation and/or (iii) pulmonary stretch, (iv) hypocapnia resulting from increased ventilation or (v) hypovolemia due to plasma volume contraction reduce parasympathetic activity in chronic hypoxia. In 13 lowlanders (8M/5F), we administered β-adrenergic blockade (intravenous propranolol) to isolate parasympathetic control of HR and thus use HR as a reciprocal index of parasympathetic activity, first at sea level (SL) and then after 9–12 days of exposure to high altitude (HA, 3800 m). Under β-adrenergic blockade, HR was 9.3 ± 6.5bpm higher at HA than at SL (P < 0.001), supporting parasympathetic withdrawal in chronic hypoxia. This HA-induced HR increase remained unchanged when (i) the arterial chemoreflex was inhibited by pure oxygen breathing (P = 0.083) but decreased when (ii) pulmonary ventilation was matched between SL and HA by paced breathing (P = 0.031). Performing apnoeas abolishing differences in pulmonary stretch (iii) did not reduce the HA-induced HR acceleration (P = 0.275), whereas (iv) increasing end-tidal CO₂ partial pressure to counteract hypocapnia at HA further enhanced it (P = 0.006). Restoring blood volume at HA to SL values by saline infusion (v) also failed to reduce the HA-induced HR acceleration (P = 0.813). Our findings support a contribution of increased ventilation, but not of arterial chemoreflex activation, hypocapnia or hypovolemia, to the parasympathetic withdrawal associated with chronic hypoxia. That performing apnoea failed to reduce the HA-induced elevation in HR furthermore indicates that the increased ventilation reduces parasympathetic activity via mechanisms other than pulmonary stretch. (Figure presented.). Key points: Chronic hypoxia reduces parasympathetic activity, but the underlying mechanisms remain unclear. At sea level and after 9–12 days of sojourn at high altitude, we used β-adrenergic blockade to isolate parasympathetic control of the heart, so that heart rate could be used as a reciprocal index for parasympathetic activity. Heart rate under β-adrenergic blockade was higher at high altitude than at sea level, supporting parasympathetic withdrawal in chronic hypoxia. Matching ventilation between sea level and high altitude reduced the high altitude-induced heart rate acceleration, indicating that the increased pulmonary ventilation in chronic hypoxia contributes to parasympathetic withdrawal. Conversely, the high altitude-induced heart rate acceleration was not reduced by inhibition of the arterial chemoreflex, or removal of hypoxia-indued hypocapnia or hypovolemia, thus not supporting these as mechanisms of reduced parasympathetic activity in chronic hypoxia.