Cerebral endothelium-dependent function and reactivity to hypercapnia: the role of α₁-adrenoreceptors

We assessed hypercapnic cerebrovascular reactivity (CVR) and endothelium-dependent function [cerebral shear-mediated dilation (cSMD)] in the internal carotid artery (ICA) with and without systemic a₁-adrenoreceptor blockade via Prazosin. We hypothesized that CVR would be reduced, whereas cSMD would remain unchanged, after Prazosin administration when compared with placebo. In 15 healthy adults (3 female, 26 ± 4 years), we conducted ICA duplex ultrasound during CVR [target + 10 mmHg partial pressure of end-tidal carbon dioxide (PET_CO2 ) above baseline, 5 min] and cSMD (+ 9 mmHg PET_CO2 above baseline, 30 s) using dynamic end-tidal forcing with and without a₁-adrenergic blockade (Prazosin; 0.05 mg/kg) in a placebo-controlled, double-blind, and randomized design. The CVR in the ICA was not different between placebo and Prazosin (P = 0.578). During CVR, the reactivities of mean arterial pressure and cerebrovascular conductance to hypercapnia were also not different between conditions (P = 0.921 and P = 0.664, respectively). During Prazosin, cSMD was lower (1.1 ± 2.0% vs 3.8 ± 3.0%; P = 0.032); however, these data should be interpreted with caution due to the elevated baseline diameter (+ 1.3 ± 3.6%; condition: P = 0.0498) and lower shear rate (-14.5 ± 23.0%; condition: P < 0.001). Therefore, lower cSMD post a₁-adrenoreceptor blockade might not indicate a reduction in cerebral endothelial function per se, but rather, that a₁-adrenoreceptors contribute to resting cerebral vascular restraint at the level of the ICA. NEW & NOTEWORTHY We assessed steady-state hypercapnic cerebrovascular reactivity and cerebral endothelium-dependent function, with and without a₁-adrenergic blockade (Prazosin), in a placebo-controlled, double-blind, and randomized study, to assess the contribution of a₁-adrenergic receptors to cerebrovascular CO₂ regulation. After administration of Prazosin, cerebrovascular reactivity to CO₂ was not different compared with placebo despite lower blood flow, whereas cerebral endothelium-dependent function was reduced, likely due to elevated baseline internal carotid arterial diameter. These findings suggest that a₁-adrenoreceptor activity does not influence cerebral blood flow regulation to CO₂ and cerebral endothelial function.