The role of myogenic mechanisms in human cerebrovascular regulation

Abstract

Key points• The autoregulatory capacity of the cerebral vasculature allows for maintenance of relatively stable blood flow in the face of fluctuating arterial pressure to protect neural tissue from wide swings in oxygen and nutrient delivery.• We recently found that neurogenic control plays an active role in autoregulation. Although myogenic pathways have also been hypothesized to play a role, previous data have not provided an unequivocal answer.• We examined cerebral blood flow responses to augmented arterial pressure oscillations with and without calcium channel blockade, and characterized autoregulation via a robust non-linear method.• Blockade significantly altered the non-linearity between pressure and flow, particularly at the slowest fluctuations, and the same rate of change in pressure elicited a larger change in flow than at baseline.• These results show that myogenic mechanisms also play a significant role in cerebrovascular regulation, and help us better understand physiological mechanisms that underlie cerebral autoregulation in humans.Abstract Although myogenic mechanisms have been hypothesized to play a role in cerebrovascular regulation, previous data from both animals and humans have not provided an unequivocal answer. However, cerebral autoregulation is explicitly non-linear and most prior work relied on simple linear approaches for assessment, potentially missing important changes in autoregulatory characteristics. Therefore, we examined cerebral blood flow responses to augmented arterial pressure oscillations with and without calcium channel blockade (nicardipine) during blood pressure fluctuations (oscillatory lower body negative pressure, OLBNP) across a range of frequencies in 16 healthy subjects. Autoregulation was characterized via a robust non-linear method (projection pursuit regression, PPR). Blockade resulted in significant tachycardia, a modest but significant elevation in mean arterial pressure, and reductions in mean cerebral blood flow and end-tidal CO 2 during OLBNP. The reductions in flow were directly related to the reductions in CO 2 (r = 0.57). While linear cross-spectral analysis showed that the relationship between pressure-flow fluctuations was preserved after blockade, PPR showed that blockade significantly altered the non-linearity between pressure and flow, particularly at the slowest fluctuations. At 0.03 Hz, blockade reduced the range of pressure fluctuations that can be buffered (7.5 ± 1.0 vs. 3.7 ± 0.8 mmHg) while increasing the autoregulatory slope (0.10 ± 0.05 vs. 0.24 ± 0.08 cm s −1 mmHg −1 ). Furthermore, the same rate of change in pressure elicited a change in flow more than twice as large as at baseline. Thus, our results show that myogenic mechanisms play a significant role in cerebrovascular regulation but this may not be appreciated without adequately characterizing the non-linearities inherent in cerebrovascular regulation.

Cerebral Vascular Control and Metabolism in Heat Stress

“…The precise mechanisms of CA remain largely controversial (11,457), and might vary from dynamic to static metrics, and from increases and decreases in MAP. Nonetheless, it is generally accepted that CA in general is mediated by the integration of metabolic, myogenic, and neurogenic factors (438,439,475). The evidence of these factors in the regulation of human CA have been recently reviewed (456 (475) (Fig.…”

Aging Impairs Myogenic Adaptation to Pulsatile Pressure in Mouse Cerebral Arteries

“…[5][6][7] In healthy young individuals the cerebral microcirculation is uniquely protected by the proximal resistance arteries of the circle of Willis and the pial arterial network, which contribute significantly to moment-to-moment regulation of cerebrovascular resistance. 8 In addition to their well-characterized role in steadystate myogenic autoregulation of cerebral blood flow (CBF; reviewed in the study by Tan et al 9 ), myogenic response of these arteries also plays a central role in dampening of pulse pressure waves, protecting the downstream microcirculation from pressure-induced injury (reviewed in the study by Vrselja et al 10 ). Although increasing evidence from clinical 4,11 and experimental studies 12,13 suggest that aging may impair local vasoregulatory mechanisms, age-related alterations in myogenic adaptation of cerebral arteries to pulsatile pressure remain elusive.…”

The Adaptive Frequency Band for Blood Pressure Variability Measurement during Nonstationary Conditions

“…On the other hand, the energy density of IMF6 and IMF7 decreases owing to the domination of Mayer wave, which is consistent to the change in LF and VLF in conventional BPV. The other intrinsic fluctuations of ABP are regulated by sympathetic nervous system, such as the changes in the peripheral resistance (0.05-0.2Hz), or regulated by the temperature regulation (0.01-0.05Hz) [7][8][9].…”

“…Lots of clinical BPV studies investigated that each frequency band indicated different neurohumoral systems mechanisms involved in non-stationary dynamic auto-regulation. Very low frequency fluctuations (VLF, 0.01-0.04Hz) indicate myogenic vascular function [8,9]. Low frequency fluctuations (LF, 0.04-0.15Hz) indicate the sympathetic nervous activities, and high frequency fluctuations (HF, 0.15-0.4Hz) indicate parasympathetic nervous activities and the release of endothelial-derived nitric oxide [3].…”