title: The effect of time-of-day and sympathetic α1-blockade on orthostatic tolerance.
abstract: Tolerance time to a standardized orthostatic stressor is markedly reduced in normotensive individuals in the morning. However, the physiological mechanisms that underpin this phenomenon are unknown. The purpose of this study was to examine the role of α(1)-adrenergic activity on orthostatic tolerance and associated cardiorespiratory and cerebrovascular responses, and to determine whether its endogenous modulation is important in the diurnal variation of orthostatic tolerance. In a four-trial, randomized placebo-controlled crossover experiment, 12 normotensive volunteers (aged 25 ± 1 yrs; mean ± SE) completed a 60° head-upward tilt (HUT; 15 min or until onset of presyncope) at 06:00 and 16:00 h, 90 min after the administration of either α(1)-blockade (prazosin, 1 mg/20 kg body weight) or placebo. Continuous beat-to-beat measurements of middle cerebral blood flow velocity (transcranial Doppler), blood pressure (Finometer), heart rate, stroke volume, cardiac output, and end-tidal carbon dioxide were obtained. Independent of time-of-day, α(1)-blockade markedly reduced the ability to tolerate a 15-min 60° HUT; tolerance time was 229% shorter compared with the placebo condition (p ≤ .0001). Moreover, a marked diurnal variation in orthostatic tolerance was evident following α(1)-adrenergic blockade; e.g., tolerance time in the morning (176 ± 30 s) was lower than in the afternoon (354 ± 75 s; p = .04). These findings highlight an important role of α(1)-sympathetic vasoconstrictor activity in acutely regulating blood pressure and offsetting syncope, especially in the early morning.
authors: School of Health and Exercise Sciences, Faculty of Health and Social Development, University of British Columbia, Okanagan Campus, Kelowna, British Columbia, Canada. Nia.Lewis@ubc.ca
authors: Nina C S
authors: NC
authors: Lewis
authors: Philip N
authors: PN
authors: Ainslie
authors: Greg
authors: G
authors: Atkinson
authors: Helen
authors: H
authors: Jones
authors: Emily J M
authors: EJ
authors: Grant
authors: Samuel J E
authors: SJ
authors: Lucas
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D018592:Cross-Over Studies; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007024:Hypotension, Orthostatic / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D011187:Posture / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D013575:Syncope / Q000209:etiology / Q000503:physiopathology*; D018667:Tilt-Table Test; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D014662:Vasoconstrictor Agents; D011224:Prazosin