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

Nia C S Lewis, Philip N. Ainslie, Greg Atkinson, Helen Jones, Emily J M Grant, Samuel J E Lucas

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    8 Citations (Scopus)


    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.

    Original languageEnglish
    JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
    Issue number2
    Publication statusPublished - 15 Jan 2013


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