title: α1-Adrenoreceptor activity does not explain lower morning endothelial-dependent, flow-mediated dilation in humans.
abstract: Early morning reduction in endothelium-dependent, flow-mediated dilation (FMD) may contribute to the high incidence of sudden cardiac death at this time of day. The mechanisms underpinning diurnal variation in FMD are unclear, but potentially relate to a circadian rhythm in sympathetic nerve activity. We hypothesized that blockade of α(1)-mediated sympathetic nerve activity would act to attenuate the diurnal variation in FMD. In a randomized and placebo-controlled design, we measured brachial artery FMD in 12 participants (mean age = 26 yr, SD = 3) at 0600 and 1600 after ingestion of an α(1)-blocker (prazosin, 1 mg/20 kg body mass) or placebo. Arterial diameter and shear rate were assessed using edge-detection software. Heart rate and blood pressure were also measured. Data were analyzed using linear mixed modeling. Following placebo, FMD was 8 ± 2% in the morning compared with 10 ± 3% in the afternoon (P = 0.04). Blockade with prazosin led to a slight but nonsignificant increase in morning FMD (P = 0.24) and a significant (P = 0.04) decrease in afternoon FMD, resulting in no diurnal variation (P = 0.20). Shear rate did not differ in the morning or afternoon under either condition (P > 0.23). Blood pressure was lower following prazosin compared with placebo (P < 0.02), an effect that was similar at both times of day (P > 0.34). Heart rate and norepinephrine levels were higher in the afternoon following prazosin. These data indicate that α(1)-adrenoreceptor activity does not explain lower morning endothelium-dependent FMD.
authors: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, United Kingdom. h.jones1@ljmu.ac.uk
authors: Helen
authors: H
authors: Jones
authors: Nia C S
authors: NC
authors: Lewis
authors: Daniel J
authors: DJ
authors: Green
authors: Philip N
authors: PN
authors: Ainslie
authors: Samuel J E
authors: SJ
authors: Lucas
authors: Yu-Chieh
authors: YC
authors: Tzeng
authors: Emily J M
authors: EJ
authors: Grant
authors: Greg
authors: G
authors: Atkinson
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D015994:Incidence; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D011224:Prazosin