Sympathetic regulation of the human cerebrovascular response to carbon dioxide

Although the cerebrovasculature is known to be exquisitely sensitive to CO₂, there is no consensus on whether the sympathetic nervous system plays a role in regulating cerebrovascular responses to changes in arterial CO₂. To address this question, we investigated human cerebrovascular CO₂ reactivity in healthy participants randomly assigned to the α₁-adrenoreceptor blockade group (9 participants; oral prazosin, 0.05 mg/kg) or the placebo control (9 participants) group. We recorded mean arterial blood pressure (MAP), heart rate (HR), mean middle cerebral artery flow velocity (MCA_{V mean}), and partial pressure of end-tidal CO₂ (PET_CO2) during 5% CO₂ inhalation and voluntary hyperventilation. CO₂ reactivity was quantified as the slope of the linear relationship between breath-to-breath PET_CO2 and the average MCA_vmean within successive breathes after accounting for MAP as a covariate. Prazosin did not alter resting HR, PET_CO2, MAP, or MCA_{V mean}. The reduction in hypocapnic CO₂ reactivity following prazosin (-0.48 ± 0.093 cm·s ^-1·mmHg^-1) was greater compared with placebo (-0.19 ± 0.087 cm·s_-1·mmHg_-1; P < 0.05 for interaction). In contrast, the change in hypercapnic CO₂ reactivity following prazosin (-0.23 cm·s_-1·mmHg _-1) was similar to placebo (-0.31 cm·s _-1·mmHg_-1; P = 0.50 for interaction). These data indicate that the sympathetic nervous system contributes to CO₂ reactivity via α₁-adrenoreceptors; blocking this pathway with prazosin reduces CO₂ reactivity to hypocapnia but not hypercapnia.