Hypoxia attenuates the respiratory response to injection of substance P into the nucleus of the solitary tract of the rat

Prolonged or repetitive bouts of hypoxia may desensitize the brain stem respiratory centres leading to reduced stimulation of ventilation. We investigated the possible involvement of changes in the sensitivity of the commissural nucleus of the solitary tract (cNTS) to the tachykinin peptide, substance P (SP). Urethane-anaesthetised rats were allowed to breath room air (normoxic) or subjected to four, 30 s bouts of hypoxia (10% O2/90% N2) prior to the injection of SP (750 pmol) into the cNTS. In normoxic rats (n = 5), SP produced a fall in frequency (f, 88 ± 4% control) after 4 min and a maximum rise in tidal volume (V(T)) after 6 min (138 ± 10% control) leading to an overall increase in minute ventilation (V(E), maximum, 127 ± 12% control after 2 min). In rats (n = 5) exposed to four bouts of hypoxia and allowed to recover for 10 min, injection of SP produced a similar fall in f but a delayed and significantly (P < 0.001) reduced V(T) (maximum after 10 min, 110 ± 1% control) and hence, V(E) response (104 ± 3% control). Sixty min after hypoxia, the f, V(T) and VE responses to SP were identical to those of normoxic rats. These data suggest that hypoxia desensitizes SP receptors in the cNTS and this may partly explain why the respiratory response to hypoxia declines over time.