1-Adrenoreceptor activity does not explain lower morning endothelial-dependent, flow-mediated dilation in humans
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.
Available from: Faris Alshammari
- "Few studies have looked at vitamin D administration in healthy young people and very few have looked at micro vascular effects of vitamin D. For example, in a study of blood flow in the fingertip (micro vascular function) vitamin D administration increased brachial artery flow mediated dilation but not fingertip blood flow . But brachial artery dilation is mediated by shear receptors which activate through microvilli and a prostaglandin mediated process including the release of nitric oxide [44–46]. The local response to occlusion is not mediated by prostaglandins or nitric oxide . "
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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.
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.
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.
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 08/2013; 19(1):641-7. DOI:10.12659/MSM.889278 · 1.43 Impact Factor
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ABSTRACT: Both cardiovascular function and dysfunction exhibit profound time-of-day-dependent oscillations. Coincident with increased sympathetic tone, vascular resistance, and pro-thrombolytic potential, the onset of myocardial infarctions occurs with greatest frequency between 6 a.m. and 12 noon. In addition, the heart exhibits poorest tolerance to ischemia/reperfusion at this time, as evidenced by the extent of cardiac injury. Temporal rhythms in both the onset and tolerance of the heart to ischemic episodes are likely the product of complex interactions between extrinsic (e.g., environmental-/behavioral-modulated) and intrinsic (e.g., circadian clock-regulated) factors. Future pharmacological strategies for myocardial infarction prevention and/or minimizing reperfusion injury should consider time-of-day-dependent rhythms in both extrinsic and intrinsic factors.
Translational Cardiology, 01/2012: pages 1-38; , ISBN: 978-1-61779-890-0
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ABSTRACT: Although the cerebrovasculature is known to be exquisitely sensitive to CO(2), there is no consensus on whether the sympathetic nervous system plays a role in regulating cerebrovascular responses to changes in arterial CO(2). To address this question, we investigated human cerebrovascular CO(2) reactivity in healthy participants randomly assigned to the α(1)-adrenoreceptor blockade group (9 participants; oral prazosin, 0.05 mg/kg) or the placebo control (9 participants) group. We recorded mean arterial blood pressure (MAP), heart rate (HR), mean middle cerebral artery flow velocity (MCA(V mean)), and partial pressure of end-tidal CO(2) (Pet(CO(2))) during 5% CO(2) inhalation and voluntary hyperventilation. CO(2) reactivity was quantified as the slope of the linear relationship between breath-to-breath Pet(CO(2)) and the average MCAv(mean) within successive breathes after accounting for MAP as a covariate. Prazosin did not alter resting HR, Pet(CO(2)), MAP, or MCA(V mean). The reduction in hypocapnic CO(2) reactivity following prazosin (-0.48 ± 0.093 cm·s(-1)·mmHg(-1)) was greater compared with placebo (-0.19 ± 0.087 cm·s(-1)·mmHg(-1); P < 0.05 for interaction). In contrast, the change in hypercapnic CO(2) reactivity following prazosin (-0.23 cm·s(-1)·mmHg(-1)) was similar to placebo (-0.31 cm·s(-1)·mmHg(-1); P = 0.50 for interaction). These data indicate that the sympathetic nervous system contributes to CO(2) reactivity via α(1)-adrenoreceptors; blocking this pathway with prazosin reduces CO(2) reactivity to hypocapnia but not hypercapnia.
Journal of Applied Physiology 06/2012; 113(5):700-6. DOI:10.1152/japplphysiol.00614.2012 · 3.06 Impact Factor
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