Influence of indomethacin on the ventilatory and cerebrovascular responsiveness to hypoxia

Indomethacin (INDO) has the potential to be a useful tool to explore the influence of cerebral blood flow and its responses to CO₂ on ventilatory control. However, the effect of INDO on the cerebrovascular and ventilatory response to hypoxia remains unclear; therefore, we examined the effect of INDO on ventilatory and cerebrovascular sensitivity to hypoxia and hypercapnia. We measured end-tidal gases, ventilation V̇_E), and middle cerebral artery velocity (MCAv) before and 90 min following INDO (100 mg) in 12 healthy participants at rest and during hyperoxic hypercapnia and isocapnic hypoxia. Following INDO, resting V̇_E and end-tidal gases were unaltered (P > 0.05), whilst MCAv was lowered by 25 ± 19% (P < 0.001). INDO ingestion reduced MCAv-CO₂ reactivity by 46 ± 29% (2.9 ± 0.9 vs. 1.7 ± 0.9 cm s^-1 mmHg ^-1; P < 0.001) and enhanced the V̇_E-CO₂ sensitivity by 0.5 ± 0.5 L min^-1 mmHg^-1 (1.9 ± 1.5 vs. 2.3 ± 1.6 L min^-1 mmHg^-1; P < 0.05). No changes were observed in either the MCAv or V̇_E responsiveness to isocapnic hypoxia following INDO ingestion (P > 0.05). These findings indicate that INDO does not alter cerebrovascular and ventilatory responsiveness to hypoxia, indicating a preserved peripheral chemoreflex in response to this pharmacological agent.