Cerebral endothelium-dependent function and reactivity to hypercapnia: the role of a1-adrenoreceptors

We assessed hypercapnic cerebrovascular reactivity (CVR) and endothelium-dependent function [cerebral shear-mediated dila-tion (cSMD)] in the internal carotid artery (ICA) with and without systemic a1-adrenoreceptor blockade via Prazosin. We hypothe-sized 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 par-tial pressure of end-tidal carbon dioxide (PETCO2) above baseline, 5 min] and cSMD (+9 mmHg PETCO2 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 condi-tions (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 indi-cate a reduction in cerebral endothelial function per se, but rather, that a1-adrenoreceptors contribute to resting cerebral vascu-lar 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, cerebro-vascular reactivity to CO2 was not different compared with placebo despite lower blood flow, whereas cerebral endothelium -de-pendent 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.