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.
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ABSTRACT: Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g., chronic mountain sickness) and methodological issues. We examined vascular function and structure in: 1) Healthy lowlanders during acute hypoxia and prolonged (~2 weeks) exposure to high altitude, and 2) High-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32±7 y) and 12 highlanders (Sherpa; 33±14 y) we assessed brachial endothelium-dependent flow mediated dilation (FMD), endothelium-independent dilation (via glyceryl trinitrate; GTN), common carotid intima thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3-4 (acute high altitude) and 12-14 (chronic high altitude) following arrival to 5050 m. Highlander were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders' FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P=0.004) and GTN-dilation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P=0.006), and raised central-PWV (6.0 ± 0.2 vs. 6.6 ± 0.3 m/s; P=0.001). These changes persisted at days 12-14, and after allometrically scaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall: lumen ratio (~19%, P≤0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and nitrite increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilation evident during acute (n=11, r=-0.53) and chronic (n=7, r=-0.69; P≤0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n=11 healthy lowlanders) conducted in a normobaric hypoxic chamber (FIO2=0.11; 6 h), a sustained reduction in FMD was evident within 1 hr of hypoxic exposure when compared to normoxic baseline (5.7 ± 1.6 vs. 8.0 ± 1.3%; P<0.01); this decline in FMD was largely reversed following α1-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high altitude exposure appears to be associated with arterial remodeling.The Journal of Physiology 12/2013; · 4.38 Impact Factor
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ABSTRACT: Background Vitamin D is a modulator of the immune system. There is some limited evidence that it also increases local blood flow in response to stress. Material and Methods In the present study, we examined 20 age matched subjects; 10 whom were from India and 10 Caucasians from the United States. Subjects were administered 4000 IU of Vitamin D3 for 3 weeks at breakfast. The function of the endothelial cells was evaluated in 2 ways; first, the response to 4 minutes of vascular occlusion was measured with a laser Doppler flow meter and second, the blood flow response to local heat at 42°C for 6 minutes. Results The results of the experiments showed that, as reported previously, the endothelial function in people from India was less than their Caucasian counterparts. The blood flow response to heat was reduced after 3 weeks administration of vitamin D in both groups and the response to vascular occlusion in the Caucasian group. But there was only a 20% reduction in the blood flow response to heat in the Caucasian group and a 50% reduction in the group from India. Conclusions Thus acute doses of vitamin D may increase vascular tone and reduce blood flow to tissue during stressors. Dosages administered for a longer duration may have beneficial effects on endothelial function but this was not examined here.Medical science monitor: international medical journal of experimental and clinical research 01/2013; 19:641-7. · 1.22 Impact Factor
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ABSTRACT: We examined whether: 1) global-cerebral blood flow (CBF) would increase across a six hours bout of normobaric poikilocapnic hypoxia and be mediated by a larger increase in blood flow in vertebral artery (VA) than in the internal carotid artery (ICA) 2); additional increases in global-CBF will be evident following an alpha (α)1-adrenergic blockade, via further dilation of the ICA and VA. In 11 young normotensive individuals, ultrasound measures of ICA- and VA-flow were obtained in normoxia (baseline) and following 60, 210 and 330 min of hypoxia (FIO2=0.11). Ninety minutes prior to final assessment, participants received a α1-adrenoreceptor blocker (Prazosin: 1 mg/20 kg body mass) or placebo. Compared to baseline, following 60, 220 and 330 min of hypoxia, global CBF [(ICAFlow + VAFlow)*2] increased by 160 ± 52 ml/min (+28%; P=0.05), 134 ± 23 ml/min (+23%; P=0.02), 113 ± 51 (+19%; P=0.27), respectively. Compared to baseline, ICAFlow increased by 23% following 60 min of hypoxia (P=0.06), after which it progressively declined. The percentage increase in VA-flow was consistently larger than ICA-flow during hypoxia by ~20% (P=0.002). Compared to baseline, ICA and VA diameters increased during hypoxia by ~9% and ~12%, respectively (P≤0.05), and were correlated to the reductions in SaO2. Flow and diameters were unaltered following α1-blockade (P≥0.10). In conclusion, elevations in global-CBF during acute hypoxia are partly mediated via greater increases in VA-flow compared to ICA-flow; this regional difference was unaltered following α1-blockade, indicating that a heightened SNA with hypoxia does not constrain further dilation of larger extracrainal blood vessels.Journal of Applied Physiology 03/2014; · 3.43 Impact Factor