Intracranial Pressure Is a Determinant of Sympathetic Activity

Schmidt, Eric; Despas, Fabien; Traon, Anne Pavy-Le; Czosnyka, Zofia; Pickard, John D.; Rahmouni, Kamal; Pathak, Atul; Senard, Jean‐Michel

doi:10.3389/fphys.2018.00011

Cited by 75 publications

(53 citation statements)

References 53 publications

(64 reference statements)

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“…) and changes in intracranial pressure (Schmidt et al . ) might all influence sympathetic outflow in HA hypoxia. Furthermore, sympathetic activation in response to elevated pulmonary artery pressure has been shown in experimental animals (Moore et al .…”

Section: Discussionmentioning

confidence: 96%

Baroreflex control of sympathetic vasomotor activity and resting arterial pressure at high altitude: insight from Lowlanders and Sherpa

Simpson

Busch

Oliver

et al. 2019

The Journal of Physiology

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Key pointsr Hypoxia, a potent activator of the sympathetic nervous system, is known to increase muscle sympathetic nerve activity (MSNA) to the peripheral vasculature of native Lowlanders during sustained high altitude (HA) exposure.r We show that the arterial baroreflex control of MSNA functions normally in healthy Lowlanders at HA, and that upward baroreflex resetting permits chronic activation of basal sympathetic vasomotor activity under this condition.r The baroreflex MSNA operating point and resting sympathetic vasomotor outflow both are lower for highland Sherpa compared to acclimatizing Lowlanders; these lower levels may represent beneficial hypoxic adaptation in Sherpa.r Acute hyperoxia at HA had minimal effect on baroreflex control of MSNA in Lowlanders and Sherpa, raising the possibility that mechanisms other than peripheral chemoreflex activation contribute to vascular sympathetic baroreflex resetting and sympathoexcitation.r These findings provide a better understanding of sympathetic nervous system activation and the control of blood pressure during the physiological stress of sustained HA hypoxia.Abstract Exposure to high altitude (HA) is characterized by heightened muscle sympathetic neural activity (MSNA); however, the effect on arterial baroreflex control of MSNA is unknown. Furthermore, arterial baroreflex control at HA may be influenced by genotypic and phenotypic differences between lowland and highland natives. Fourteen Lowlanders (12 male) and nine male Sherpa underwent haemodynamic and sympathetic neural assessment at low altitude (Lowlanders, low altitude; 344 m, Sherpa, Kathmandu; 1400 m) and following gradual ascent to L. L. Simpson and others J Physiol 597.9 5050 m. Beat-by-beat haemodynamics (photoplethysmography) and MSNA (microneurography) were recorded lying supine. Indices of vascular sympathetic baroreflex function were determined from the relationship of diastolic blood pressure (DBP) and corresponding MSNA at rest (i.e. DBP 'operating pressure' and MSNA 'operating point'), as well as during a modified Oxford baroreflex test (i.e. 'gain'). Operating pressure and gain were unchanged for Lowlanders during HA exposure; however, the operating point was reset upwards (48 ± 16 vs. 22 ± 12 bursts 100 HB −1 , P = 0.001). Compared to Lowlanders at 5050 m, Sherpa had similar gain and operating pressure, although the operating point was lower (30 ± 13 bursts 100 HB −1 , P = 0.02); MSNA burst frequency was lower for Sherpa (22 ± 11 vs. 30 ± 9 bursts min −1 P = 0.03). Breathing 100% oxygen did not alter vascular sympathetic baroreflex function for either group at HA. For Lowlanders, upward baroreflex resetting promotes heightened sympathetic vasoconstrictor activity and maintains blood pressure stability, at least during early HA exposure; mechanisms other than peripheral chemoreflex activation could be involved. Sherpa adaptation appears to favour a lower sympathetic vasoconstrictor activity compared to Lowlanders for blood pressure homeostasis.

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Section: Discussionmentioning

confidence: 96%

Baroreflex control of sympathetic vasomotor activity and resting arterial pressure at high altitude: insight from Lowlanders and Sherpa

Simpson

Busch

Oliver

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…Thus, extrapolation to a normal range of ICP has remained problematic. Several previous studies have postulated the existence of a novel physiological intracranial reflex controlling sympathetic nerve activity and BP (4,16,18,24); however, in lieu of a lack of supporting experimental data, these ideas have remained theoretical. Our data support the hypothesis that ICP can act to determine sympathetic activity and BP in the normal physiological setting.…”

Section: Discussionmentioning

confidence: 99%

Intracranial pressure influences the level of sympathetic tone

Guild

Saxena²,

McBryde

et al. 2018

American Journal of Physiology-Regulatory, Integrative and Comp

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Sympathetic overdrive is associated with many diseases, but its origin remains an enigma. An emerging hypothesis in the development of cardiovascular disease is that the brain puts the utmost priority on maintaining its own blood supply; even if this comes at the "cost" of high blood pressure to the rest of the body. A critical step in making a causative link between reduced brain blood flow and cardiovascular disease is how changes in cerebral perfusion affect the sympathetic nervous system. A direct link between decreases in cerebral perfusion pressure and sympathetic tone generation in a conscious large animal has not been shown. We hypothesized that there is a novel control pathway between physiological levels of intracranial pressure (ICP) and blood pressure via the sympathetic nervous system. Intracerebroventricular infusion of saline produced a ramped increase in ICP of up to 20 mmHg over a 30-minute infusion period (baseline 4.0±1.1 mmHg). The ICP increase was matched by an increase mean arterial pressure such that cerebral perfusion pressure remained constant. Direct recordings of renal sympathetic nerve activity indicated that sympathetic drive increased with increasing ICP. Ganglionic blockade, by hexamethonium, preventing sympathetic transmission, abolished the increase in arterial pressure in response to increased ICP and was associated with a significant decrease in cerebral perfusion pressure. This is the first study to show that physiological elevations in intracranial pressure regulate renal sympathetic activity in conscious animals. We have demonstrated a novel physiological mechanism linking ICP levels with sympathetic discharge via a possible novel intracranial baroreflex.

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“…5). The mechanism(s) underpinning the increase in sympathetic neural outflow during hypoxia exposure remains unclear; however, there is evidence that elevated peripheral chemoreflex drive (Somers et al 1989), red blood cell production (Oshima et al 2018), intracranial pressure (Schmidt et al 2018) and pulmonary artery pressure (Moore et al 2011) may be responsible. It is worth noting, the mechanism(s) responsible for sympathetic nerve 'hyper'-activity in hypoxia seem to be influenced by the length of exposure; for example, the peripheral chemoreflex has been shown to mediate increases in SNA during acute (Somers et al 1989), but not chronic exposure (Hansen & Sander, 2003;Fisher et al 2018;Simpson et al 2019).…”

Section: Sympathetic Nerve Activitymentioning

confidence: 99%

The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations

Tymko

Tremblay

Bailey

et al. 2019

The Journal of Physiology

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Exposure to hypoxia elicits widespread physiological responses that are critical for successful acclimatization; however, these responses may induce apparent maladaptive consequences. For example, recent studies conducted in both the laboratory and the field (e.g. at high altitude) have demonstrated that endothelial function is reduced in hypoxia. Herein, we review the several proposed mechanism(s) pertaining to the observed reduction in endothelial function in hypoxia including: (i) changes in blood flow patterns (i.e. shear stress), (ii) increased inflammation and production of reactive oxygen species (i.e. oxidative stress), (iii) heightened sympathetic nerve activity, and (iv) increased red blood cell concentration and mass leading to elevated nitric oxide scavenging. Although some of these mechanism(s) have been examined in lowlanders, less in known about endothelial function in indigenous populations that have chronically adapted to environmental hypoxia for millennia (e.g. the Peruvian, Tibetan and Ethiopian highlanders). There is some evidence indicating that healthy Tibetan and Peruvian (i.e. Andean) highlanders have preserved endothelial function at high altitude, but less is known about the Ethiopian highlanders. However, Andean highlanders suffering from chronic mountain sickness, which is characterized by an excessive production of red blood cells, have markedly reduced endothelial function. This review will provide a framework and mechanistic model for vascular endothelial adaptation to hypoxia in lowlanders and highlanders. Elucidating the pathways responsible for vascular adaption/maladaptation to hypoxia has potential clinical implications for disease featuring low oxygen delivery (e.g. heart failure, pulmonary disease). In addition, a greater understanding of vascular function at high altitude will clinically benefit the global estimated 85 million high altitude residents.

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Intracranial Pressure Is a Determinant of Sympathetic Activity

Cited by 75 publications

References 53 publications

Baroreflex control of sympathetic vasomotor activity and resting arterial pressure at high altitude: insight from Lowlanders and Sherpa

Baroreflex control of sympathetic vasomotor activity and resting arterial pressure at high altitude: insight from Lowlanders and Sherpa

Intracranial pressure influences the level of sympathetic tone

The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations

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