α1-Adrenergic receptor control of the cerebral vasculature in humans at rest and during exercise

We tested the hypothesis that pharmacological blockade of alpha(1)-adrenoreceptors (by prazosin), at rest and during steady-state dynamic exercise, would impair cerebral autoregulation and result in cerebral vasodilatation in healthy humans. In 10 subjects, beat-to-beat mean arterial pressure and mean middle cerebral artery blood velocity were determined at rest and during low (Ex90) and moderate workload (Ex130) on an upright bicycle ergometer without and with prazosin. Plasma noradrenaline concentrations increased significantly from rest to Ex130 during control conditions (from 1.8 +/- 0.2 to 3.2 +/- 0.3 pmol (ml plasma)(-1)). In the control conditions, the transfer function gain between mean arterial pressure and mean middle cerebral artery blood velocity in the low-frequency range was decreased at Ex90 (P = 0.035) and Ex130 (P = 0.027) from rest. A significant increase in critical closing pressure (CCP) was also observed in the control conditions from rest to Ex90 to Ex130 (from 18 +/- 3 to 24 +/- 4 to 31 +/- 4 mm Hg). An average of 74 +/- 2% blockade of blood pressure response was achieved with oral prazosin. Following blockade, plasma noradrenaline concentrations further increased at rest and during Ex130 from the control value (from 2.6 +/- 0.3 to 4.4 +/- 0.5 pmol (ml plasma)(-1)). Prazosin also resulted in an increase in low-frequency gain (P < 0.003) compared with the control conditions. Prazosin blockade abolished the increases in CCP during Ex130 and increased the cerebrovascular conductance index (P = 0.018). These data indicate that in the control conditions a strengthening of cerebral autoregulation occurred with moderate dynamic exercise that is associated with an increase in CCP as a result of the exercise-mediated augmentation of sympathetic activity. Given that alpha(1)-adrenergic receptor blockade attenuated the increase in dynamic cerebral autoregulation and CCP, we conclude that increases in sympathetic activity have a role in establishing cerebral vascular tone in humans.