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Blood pressure (BP) regulation is widely recognized as being integral to the control of end-organ perfusion, but it remains unclear whether end-organ perfusion also plays a role in driving changes in BP. A randomized and placebocontrolled study design was followed to examine feedback relationships between very-low-frequency fluctuations in BP and cerebral blood flow (CBF) in humans under placebo treatment and α1-adrenergic blockade. To determine the causal relations among hemodynamic variables, BP, middle cerebral artery blood velocity (MCAv), and end-tidal CO 2 time-series were decimated, low-pass filtered (<0.07 Hz), fitted to vector autoregressive models, and tested for Granger causality in the time domain. Results showed that 1) at baseline, changes in BP and MCAv often interact in a closed-loop; and 2) α1-adrenergic blockade results in the dominant causal direction from BP to MCAv. These results suggest that, between subjects, cerebral pressure-flow interactions at time scales < 0.07 Hz are frequently bidirectional, and that in the presence of an intact autonomic nervous system BP may be regulated by reflex pathways sensitive to changes in CBF. [ABSTRACT FROM AUTHOR]

Resting vascular sympathetic outflow is significantly increased during and beyond exposure to acute hypoxia without a parallel increase in either resistance or pressure. This uncoupling may indicate a reduction in the ability of sympathetic outflow to effect vascular responses (sympathetic transduction). However, the effect of hypoxia on sympathetic transduction has not been explored. We hypothesized that transduction would either remain unchanged or be reduced by isocapnic hypoxia. In 11 young healthy individuals, we measured beat-by-beat pressure, multiunit sympathetic nerve activity, and popliteal blood flow velocity at rest and during isometric handgrip exercise to fatigue, before and during isocapnic hypoxia (~80% SpO2), and derived sympathetic transduction for each subject via a transfer function that reflects Poiseuille's law of flow. During hypoxia, heart rate and sympathetic nerve activity increased, whereas pressure and flow remained unchanged. Both normoxic and hypoxic exercise elicited significant increases in heart rate, pressure, and sympathetic activity, although sympathetic responses to hypoxic exercise were blunted. Hypoxia slightly increased the gain relation between pressure and flow (0.062 ± 0.006 vs. 0.074 ± 0.004 cm·s-1·mmHg-1; P = 0.04), but markedly increased sympathetic transduction (-0.024 ± 0.005 vs. -0.042 ± 0.007 cm·s-1·spike-1; P < 0.01). The pressor response to isometric handgrip was similar during normoxic and hypoxic exercise due to the balance of interactions among the tachycardia, sympathoexcitation, and transduction. This indicates that the ability of sympathetic activity to affect vasoconstriction is enhanced during brief exposure to isocapnic hypoxia, and this appears to offset the potent vasodilatory stimulus of hypoxia. [ABSTRACT FROM AUTHOR]

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 α1-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 α1-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 α1-adrenoreceptor activity does not explain lower morning endothelium-dependent FMD. [ABSTRACT FROM AUTHOR]