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 ste m respiratory centres leading to reduced stimulation of ventilation. W e investigated the possible involvement of changes in the sensitivity of the commissural nucleus of the solitary tract (cNTS) to the tachyki nin peptide, substance P (SP). Urethane-anaesthetised rats were allowe d to breath room air (normoxic) or subjected to four, 30 s bouts of hy poxia (10% O-2/90% N-2) prior to the injection of SP (750 pmol) into t he 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). I n 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 delaye d and significantly (P < 0.001) reduced V-T (maximum after 10 min, 110 +/- 11% control) and hence, V-E response (104 +/- 3% control). Sixty min after hypoxia, the f, V-T and V-E responses to SP were identical t o those of normoxic rats. These data suggest that hypoxia desensitizes SP receptors in the cNTS and this may partly explain why the respirat ory response to hypoxia declines over time. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.