Initial orthostatic hypotension and cerebral blood flow regulation: Effect of α1-adrenoreceptor activity

We examined the hypothesis that α₁-adrenergic blockade would lead to an inability to correct initial orthostatic hypotension (IOH) and cerebral hypoperfusion, leading to symptoms of presyncope. Twelve normotensive humans (aged 25 ± 1 yr; means ± SE) attempted to complete a 3-min upright stand, 90 min after the administration of either α₁-blockade (prazosin, 1 mg/20 kg body wt) or placebo. Continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv; Doppler), blood pressure (finometer), heart rate, and end-tidal PCO₂ were obtained. Compared with placebo, the α₁-blockade reduced resting mean arterial blood pressure (MAP) (-15%; P < 0.01); MCAv remained unaltered (P ≥ 0.28). Upon standing, although the absolute level of MAP was lower following α₁-blockade (39 ± 10 mmHg vs. 51 ± 14 mmHg), the relative difference in IOH was negligible in both trials (mean difference in MAP: 2 ± 2 mmHg; P = 0.50). Compared with the placebo trial, the declines in MCAv and PETCO₂ during IOH were greater in the α₁-blockade trial by 12 ± 4 cm/s and 4.4 ± 1.3 mmHg, respectively (P ≤ 0.01). Standing tolerance was markedly reduced in the α₁-blockade trial (75 ± 17 s vs. 180 ± 0 s; P < 0.001). In summary, while IOH was little affected by α₁-blockade, the associated decline in MCAv was greater in the blockade condition. Unlike in the placebo trial, the extent of IOH and cerebral hypoperfusion failed to recover toward baseline in the α₁-blockade trial leading to presyncope. Although the development of IOH is not influenced by the α₁-adrenergic receptor pathway, this pathway is critical in the recovery from IOH to prevent cerebral hypoperfusion and ultimately syncope.