Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans

An important determinant of [H⁺]in the environment of the central chemoreceptors is cerebral blood flow. Accordingly we hypothesized that a reduction of brain perfusion or a reduced cerebrovascular reactivity to CO₂ would lead to hyperventilation and an increased ventilatory responsiveness to CO₂. We used oral indomethacin to reduce the cerebrovascular reactivity to CO₂ and tested the steady-state hypercapnic ventilatory response to CO₂ in nine normal awake human subjects under normoxia and hyperoxia (50%O₂). Ninety minutes after indomethacin ingestion, cerebral blood flow velocity (CBFV) in the middle cerebral artery decreased to 77 ± 5% of the initial value and the average slope of CBFV response to hypercapnia was reduced to 31 of control in normoxia (1.92 versus 0.59 cm^-1 s^-1 mmHg^-1, P < 0.05) and 37%; of control in hyperoxia (1.58 versus 0.59 cm^-1 s^-1 mmHg^-1, P < 0.05). Concomitantly, indomethacin administration also caused 40-60%, increases in the slope of the mean ventilatory response to CO₂ in both normoxia (1.27 ± 0.31 versus 1.76 ± 0.37 l min^-1 mmHg^-1, P < 0.05) and hyperoxia (1.08 ± 0.22 versus 1.79 ± 0.37 l min^-1 mmHg^-1, P < 0.05). These correlative findings are consistent with the conclusion that cerebrovascular responsiveness to CO₂ is an important determinant of eupnoeic ventilation and of hypercapnic ventilatory responsiveness in humans, primarily via its effects at the level of the central chemoreceptors.