Sympathetic regulation of the human cerebrovascular response to carbon dioxide

<jats:p> Although the cerebrovasculature is known to be exquisitely sensitive to CO<jats:sub>2</jats:sub>, there is no consensus on whether the sympathetic nervous system plays a role in regulating cerebrovascular responses to changes in arterial CO<jats:sub>2</jats:sub>. To address this question, we investigated human cerebrovascular CO<jats:sub>2</jats:sub> reactivity in healthy participants randomly assigned to the α<jats:sub>1</jats:sub>-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<jats:sub>V mean</jats:sub>), and partial pressure of end-tidal CO<jats:sub>2</jats:sub> (Pet<jats:sub>CO<jats:sub>2</jats:sub></jats:sub>) during 5% CO<jats:sub>2</jats:sub> inhalation and voluntary hyperventilation. CO<jats:sub>2</jats:sub> reactivity was quantified as the slope of the linear relationship between breath-to-breath Pet<jats:sub>CO<jats:sub>2</jats:sub></jats:sub> and the average MCAv<jats:sub>mean</jats:sub> within successive breathes after accounting for MAP as a covariate. Prazosin did not alter resting HR, Pet<jats:sub>CO<jats:sub>2</jats:sub></jats:sub>, MAP, or MCA<jats:sub>V mean</jats:sub>. The reduction in hypocapnic CO<jats:sub>2</jats:sub> reactivity following prazosin (−0.48 ± 0.093 cm·s<jats:sup>−1</jats:sup>·mmHg<jats:sup>−1</jats:sup>) was greater compared with placebo (−0.19 ± 0.087 cm·s<jats:sup>−1</jats:sup>·mmHg<jats:sup>−1</jats:sup>; P < 0.05 for interaction). In contrast, the change in hypercapnic CO<jats:sub>2</jats:sub> reactivity following prazosin (−0.23 cm·s<jats:sup>−1</jats:sup>·mmHg<jats:sup>−1</jats:sup>) was similar to placebo (−0.31 cm·s<jats:sup>−1</jats:sup>·mmHg<jats:sup>−1</jats:sup>; P = 0.50 for interaction). These data indicate that the sympathetic nervous system contributes to CO<jats:sub>2</jats:sub> reactivity via α<jats:sub>1</jats:sub>-adrenoreceptors; blocking this pathway with prazosin reduces CO<jats:sub>2</jats:sub> reactivity to hypocapnia but not hypercapnia. </jats:p>