ORCID Profile
0000-0001-7851-9222
Current Organisations
The University of Auckland
,
University of Birmingham
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Publisher: Wiley
Date: 14-04-2023
DOI: 10.1113/JP284249
Abstract: Increased peripheral chemoreflex sensitivity is a pathogenic feature of human hypertension (HTN), while both central and peripheral chemoreflex sensitivities are reportedly augmented in animal models of HTN. Herein, we tested the hypothesis that both central and combined central and peripheral chemoreflex sensitivities are augmented in HTN. Fifteen HTN participants (68 ± 5 years mean ± SD) and 13 normotensives (NT 65 ± 6 years) performed two modified rebreathing protocols in which the partial pressure of end‐tidal carbon dioxide () progressively increased while the partial pressure of end‐tidal oxygen was cl ed at either 150 mmHg (isoxic hyperoxia central chemoreflex activation) or 50 mmHg (isoxic hypoxia combined central and peripheral chemoreflex activation). Ventilation ( pneumotachometer) and muscle sympathetic nerve activity (MSNA microneurography) were recorded, and ventilatory ( vs . slope) and sympathetic (MSNA vs . slope) chemoreflex sensitivities and recruitment thresholds (breakpoint) were calculated. Global cerebral blood flow (gCBF duplex Doppler) was measured, and the association with chemoreflex responses was examined. Central ventilatory and sympathetic chemoreflex sensitivities were greater in HTN than NT (2.48 ± 1.33 vs . 1.58 ± 0.42 L min −1 mmHg −1 , P = 0.030: 3.32 ± 1.90 vs . 1.77 ± 0.62 a.u. mmHg −1 , P = 0.034, respectively), while recruitment thresholds were not different between groups. HTN and NT had similar combined central and peripheral ventilatory and sympathetic chemoreflex sensitivities and recruitment thresholds. A lower gCBF was associated with an earlier recruitment threshold for ( R 2 = 0.666, P 0.0001) and MSNA ( R 2 = 0.698, P = 0.004) during isoxic hyperoxic rebreathing. These findings indicate that central ventilatory and sympathetic chemoreflex sensitivities are augmented in human HTN and perhaps suggest that targeting the central chemoreflex may help some forms of HTN. image In human hypertension (HTN) increased peripheral chemoreflex sensitivity has been identified as a pathogenic feature, and in animal models of HTN, both central and peripheral chemoreflex sensitivities are reportedly augmented. In this study, the hypothesis was tested that both central and combined central and peripheral chemoreflex sensitivities are augmented in human HTN. We observed that both central ventilatory and sympathetic chemoreflex sensitivities were augmented in HTN compared to age‐matched normotensive controls, but no difference was found in the combined central and peripheral ventilatory and sympathetic chemoreflex sensitivities. During central chemoreflex activation, the ventilatory and sympathetic recruitment thresholds were lower in those with lower total cerebral blood flow. These results indicate a potential contributory role of the central chemoreceptors in the pathogenesis of human HTN and support the possibility that therapeutic targeting of the central chemoreflex may help some forms of HTN.
Publisher: Wiley
Date: 31-01-2013
Publisher: Wiley
Date: 28-01-2022
DOI: 10.1113/JP282707
Publisher: Wiley
Date: 11-2014
DOI: 10.1111/MICC.12155
Abstract: The effects of RT on muscle mass, strength, and insulin sensitivity are well established, but the underlying mechanisms are only partially understood. The main aim of this study was to investigate whether RT induces changes in endothelial enzymes of the muscle microvasculature, which would increase NO bioavailability and could contribute to improved insulin sensitivity. Eight previously sedentary males (age 20 ± 0.4 years, BMI 24.5 ± 0.9 kg/m(2) ) completed six weeks of RT 3x/week. Muscle biopsies were taken from the m. vastus lateralis and microvascular density and endothelial-specific eNOS content, eNOS Ser(1177) phosphorylation, and NOX2 content were assessed pre- and post-RT using quantitative immunofluorescence microscopy. Whole-body insulin sensitivity (measured as Matsuda Index), microvascular Kf (functional measure of the total available endothelial surface area), and arterial stiffness (AIx, central, and pPWV) were also measured. Measures of microvascular density, microvascular Kf , microvascular eNOS content, basal eNOS phosphorylation, and endothelial NOX2 content did not change from pre-RT to post-RT. RT increased insulin sensitivity (p < 0.05) and reduced resting blood pressure and AIx (p < 0.05), but did not change central or pPWV. RT did not change any measure of muscle microvascular structure or function.
Publisher: Springer Science and Business Media LLC
Date: 27-05-2010
DOI: 10.1038/JHH.2010.53
Abstract: An exaggerated blood pressure (BP) response to exercise predicts future cardiovascular risk. The mechanisms underlying exercise-induced hypertension remain unclear, although endothelial dysfunction and elevated arterial stiffness may contribute. Given the association between reductions in nitric oxide (NO) and vascular dysfunction, we sought to determine whether acute inhibition of NO synthase with N(G)-monomethyl-L-arginine (L-NMMA) would lead to exaggerated BP responses to maximal exercise and attenuate exercise-induced reductions in arterial stiffness. In 10 healthy subjects (31±5 years), BP and heart rate (HR) were measured before, during and after an incremental cycling exercise test to determine maximal oxygen consumption (VO(2)max). Trials were performed with placebo (saline) or intravenous infusion of L-NMMA on separate days in a randomized, double-blind, crossover design. Central (aortic) and peripheral (femoral) arterial stiffness were assessed using pulse wave velocity (PWV). BP was increased with L-NMMA at rest and during sub-maximal exercise, but not at maximal exercise (mean BP 117±5 vs 118±8 mm Hg, saline vs L-NMMA, P>0.05). Furthermore, L-NMMA had no influence on exercising HR or VO(2)max (P<0.05). Notably, aortic PWV was similarly increased after exercise with either saline or L-NMMA (P<0.05), whereas postexercise decreases in femoral PWV were attenuated with L-NMMA (P<0.05). Our findings suggest that NO is an important contributor to reductions in femoral artery stiffness after maximal exercise in healthy in iduals. Furthermore, acute pharmacological inhibition of NO synthase causes augmented BP responses to sub-maximal exercise, but does not lead to exaggerated BP responses to maximal exercise or reduce maximal oxygen consumption.
Publisher: Wiley
Date: 24-02-2015
Publisher: American Physiological Society
Date: 06-2023
DOI: 10.1152/JAPPLPHYSIOL.00670.2022
Abstract: Hypertension remains a significant global health problem. Although hypertension research and therapies are keenly focused on the heart and arterial circulation, the venous circulation has been neglected comparatively. We determined whether hypoxia, known to cause peripheral chemoreflex activation, evoked more pronounced changes in lower limb venous capacity and compliance in hypertensives (HTN) than in age-matched normotensives (NT). We found that hypoxia reduced venous capacity in the great saphenous vein in HTN and increased its compliance twofold. However, hypoxia did not affect venous function in NT. Our data indicate the venomotor response to hypoxia is enhanced in hypertension, and this may contribute to the hypertensive state.
Publisher: Wiley
Date: 12-05-2022
DOI: 10.1113/JP282327
Abstract: The purpose of this study was to determine whether there are sex differences in the cardiorespiratory and sympathetic neurocirculatory responses to central, peripheral, and combined central and peripheral chemoreflex activation. Ten women (29 ± 6 years, 22.8 ± 2.4 kg/m 2 : mean ± SD) and 10 men (30 ± 7 years, 24.8 ± 3.2 kg/m 2 ) undertook randomized 5 min breathing trials of: room air (eucapnia), isocapnic hypoxia (10% oxygen (O 2 ) peripheral chemoreflex activation), hypercapnic hyperoxia (7% carbon dioxide (CO 2 ), 50% O 2 central chemoreflex activation) and hypercapnic hypoxia (7% CO 2 , 10% O 2 central and peripheral chemoreflex activation). Control trials of isocapnic hyperoxia (peripheral chemoreflex inhibition) and hypocapnic hyperoxia (central and peripheral chemoreflex inhibition) were also included. Muscle sympathetic nerve activity (MSNA microneurography), mean arterial pressure (MAP finger photoplethysmography) and minute ventilation ( E pneumotachometer) were measured. Total MSNA ( P = 1.000 and P = 0.616), MAP ( P = 0.265) and E ( P = 0.587 and P = 0.472) were not different in men and women during eucapnia and during isocapnic hypoxia. Women exhibited attenuated increases in E during hypercapnic hyperoxia (27.3 ± 6.3 vs . 39.5 ± 7.5 l/min, P 0.0001) and hypercapnic hypoxia (40.9 ± 9.1 vs . 53.8 ± 13.3 l/min, P 0.0001) compared with men. However, total MSNA responses were augmented in women (hypercapnic hyperoxia 378 ± 215 vs . 258 ± 107%, P = 0.017 hypercapnic hypoxia 607 ± 290 vs . 362 ± 268%, P 0.0001). No sex differences in total MSNA, MAP or E were observed during isocapnic hyperoxia and hypocapnic hyperoxia. Our results indicate that young women have augmented sympathetic responses to central chemoreflex activation, which explains the augmented MSNA response to combined central and peripheral chemoreflex activation. Sex differences in the control of breathing have been well studied, but whether there are differences in the sympathetic neurocirculatory responses to chemoreflex activation between healthy women and men is incompletely understood. We observed that, compared with young men, young women displayed augmented increases in muscle sympathetic nerve activity during both hypercapnic hyperoxia (central chemoreflex activation) and hypercapnic hypoxia (central and peripheral chemoreflex activation) but had attenuated increases in minute ventilation. In contrast, no sex differences were found in either muscle sympathetic nerve activity or minute ventilation responses to isocapnic hypoxia (peripheral chemoreceptor stimulation). Young women have blunted ventilator, but augmented sympathetic responses, to central (hypercapnic hyperoxia) and combined central and peripheral chemoreflex activation (hypercapnic hypoxia), compared with young men. The possible causative association between the reduced ventilation and heightened sympathetic responses in young women awaits validation.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2020
End Date: 2023
Funder: Marsden Fund
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