Sympathetic regulation of the human cerebrovascular response to carbon dioxide

Abstract

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 (MCAV mean), and partial pressure of end-tidal CO2 (PetCO2) during 5% CO2 inhalation and voluntary hyperventilation. CO2 reactivity was quantified as the slope of the linear relationship between breath-to-breath PetCO2 and the average MCAvmean within successive breathes after accounting for MAP as a covariate. Prazosin did not alter resting HR, PetCO2, MAP, or MCAV 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.