14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans

Short-term intermittent hypoxia leads to sustained sympathetic activation and a small increase in blood pressure in healthy humans. Because obstructive sleep apnea, a condition associated with intermittent hypoxia, is accompanied by elevated sympathetic activity and enhanced sympathetic chemoreflex responses to acute hypoxia, we sought to determine whether intermittent hypoxia also enhances chemoreflex activity in healthy humans. To this end, we measured the responses of muscle sympathetic nerve activity (MSNA, peroneal microneurography) to arterial chemoreflex stimulation and deactivation before and following exposure to a paradigm of repetitive hypoxic apnea (20 s/min for 30 min; O2 saturation nadir 81.4 ± 0.9%). Compared with baseline, repetitive hypoxic apnea increased MSNA from 113 ± 11 to 159 ± 21 units/min ( P = 0.001) and mean blood pressure from 92.1 ± 2.9 to 95.5 ± 2.9 mmHg ( P = 0.01; n = 19). Furthermore, compared with before, following intermittent hypoxia the MSNA (units/min) responses to acute hypoxia [fraction of inspired O2 (FiO2) 0.1, for 5 min] were enhanced (pre- vs. post-intermittent hypoxia: +16 ± 4 vs. +49 ± 10%; P = 0.02; n = 11), whereas the responses to hyperoxia (FiO2 0.5, for 5 min) were not changed significantly ( P = NS; n = 8). Thus 30 min of intermittent hypoxia is capable of increasing sympathetic activity and sensitizing the sympathetic reflex responses to hypoxia in normal humans. Enhanced sympathetic chemoreflex activity induced by intermittent hypoxia may contribute to altered neurocirculatory control and adverse cardiovascular consequences in sleep apnea.

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Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00253.2009 ◽

2010 ◽

Vol 299 (3) ◽

pp. H925-H931 ◽

Cited By ~ 73

Author(s):

G. S. Gilmartin ◽

M. Lynch ◽

R. Tamisier ◽

J. W. Weiss

Keyword(s):

Blood Pressure ◽

Sympathetic Nerve ◽

Intermittent Hypoxia ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Chronic Intermittent Hypoxia ◽

Sympathetic Activation ◽

Nerve Activity ◽

Blood Pressure Elevation ◽

Healthy Humans

Chronic intermittent hypoxia (CIH) is thought to be responsible for the cardiovascular disease associated with obstructive sleep apnea (OSA). Increased sympathetic activation, altered vascular function, and inflammation are all putative mechanisms. We recently reported (Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas RJ, Levy P, Weiss JW. J Appl Physiol 107: 17–24, 2009) a new model of CIH in healthy humans that is associated with both increases in blood pressure and augmented peripheral chemosensitivity. We tested the hypothesis that exposure to CIH would also result in augmented muscle sympathetic nerve activity (MSNA) and altered vascular reactivity contributing to blood pressure elevation. We therefore exposed healthy subjects between the ages of 20 and 34 yr ( n = 7) to 9 h of nocturnal intermittent hypoxia for 28 consecutive nights. Cardiovascular and hemodynamic variables were recorded at three time points; MSNA was collected before and after exposure. Diastolic blood pressure (71 ± 1.3 vs. 74 ± 1.7 mmHg, P < 0.01), MSNA [9.94 ± 2.0 to 14.63 ± 1.5 bursts/min ( P < 0.05); 16.89 ± 3.2 to 26.97 ± 3.3 bursts/100 heartbeats (hb) ( P = 0.01)], and forearm vascular resistance (FVR) (35.3 ± 5.8 vs. 55.3 ± 6.5 mmHg·ml−1·min·100 g tissue, P = 0.01) all increased significantly after 4 wk of exposure. Forearm blood flow response following ischemia of 15 min (reactive hyperemia) fell below baseline values after 4 wk, following an initial increase after 2 wk of exposure. From these results we conclude that the increased blood pressure following prolonged exposure to CIH in healthy humans is associated with sympathetic activation and augmented FVR.

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Effects of selective slow-wave sleep deprivation on nocturnal blood pressure dipping and daytime blood pressure regulation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00368.2009 ◽

2010 ◽

Vol 298 (1) ◽

pp. R191-R197 ◽

Cited By ~ 55

Author(s):

Friedhelm Sayk ◽

Christina Teckentrup ◽

Christoph Becker ◽

Dennis Heutling ◽

Peter Wellhöner ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Slow Wave ◽

Slow Wave Sleep ◽

Muscle Sympathetic Nerve Activity ◽

Catecholamine Excretion ◽

Nocturnal Blood Pressure ◽

Healthy Humans ◽

Daytime Blood Pressure ◽

Nocturnal Blood Pressure Dipping

Nocturnal blood pressure (BP) decline or “dipping” is an active, central, nervously governed process, which is important for BP regulation during daytime. It is, however, not known whether the sleep process itself or, more specifically, slow-wave sleep (SWS) is important for normal dipping. Therefore, in the present study, healthy subjects (6 females, 5 males) were selectively deprived of SWS by EEG-guided acoustic arousals. BP and heart rate (HR) were monitored during experimental nights and the following day. Additionally, nocturnal catecholamine excretion was determined, and morning baroreflex function was assessed by microneurographic measurements of muscle sympathetic nerve activity (MSNA) and heart rate variability (HRV). Data were compared with a crossover condition of undisturbed sleep. SWS was successfully deprived leading to significantly attenuated mean arterial BP dipping during the first half ( P < 0.05), but not during the rapid-eye-movement-dominated second half of total sleep; however, dipping still evolved even in the absence of SWS. No differences were found for nighttime catecholamine excretion. Moreover, daytime resting and ambulatory BP and HR were not altered, and morning MSNA and HRV did not differ significantly, indicating that baroreflex-mediated sympathoneural BP regulation was not affected by the preceding SWS deprivation. We conclude that in healthy humans the magnitude of nocturnal BP dipping is significantly affected by sleep depth. Deprivation of SWS during one night does not modulate the morning threshold and sensitivity of the vascular and cardiac baroreflex and does not alter ambulatory BP during daytime.

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Endurance training attenuates the increase in peripheral chemoreflex sensitivity with intermittent hypoxia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00105.2016 ◽

2017 ◽

Vol 312 (2) ◽

pp. R223-R228 ◽

Cited By ~ 3

Author(s):

Amanda J. Miller ◽

Charity L. Sauder ◽

Aimee E. Cauffman ◽

Cheryl A. Blaha ◽

Urs A. Leuenberger

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Endurance Training ◽

Intermittent Hypoxia ◽

Muscle Sympathetic Nerve Activity ◽

Interval Training ◽

Control Subjects ◽

Healthy Humans ◽

Chemoreflex Sensitivity ◽

Peripheral Chemoreflex

Patients with heart failure and sleep apnea have greater chemoreflex sensitivity, presumably due to intermittent hypoxia (IH), and this is predictive of mortality. We hypothesized that endurance training would attenuate the effect of IH on peripheral chemoreflex sensitivity in healthy humans. Fifteen young healthy subjects (9 female, 26 ± 1 yr) participated. Between visits, 11 subjects underwent 8 wk of endurance training that included running four times/wk at 80% predicted maximum heart rate and interval training, and four control subjects did not change activity. Chemoreflex sensitivity (the slope of ventilation responses to serial oxygen desaturations), blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were assessed before and after 30 min of IH. Endurance training decreased resting systolic blood pressure (119 ± 3 to 113 ± 3 mmHg; P = 0.027) and heart rate (67 ± 3 to 61 ± 2 beats/min; P = 0.004) but did not alter respiratory parameters at rest ( P > 0.2). Endurance training attenuated the IH-induced increase in chemoreflex sensitivity (pretraining: Δ 0.045 ± 0.026 vs. posttraining: Δ −0.028 ± 0.040 l·min−1·% O2 desaturation−1; P = 0.045). Furthermore, IH increased mean blood pressure and MSNA burst rate before training ( P < 0.05), but IH did not alter these measures after training ( P > 0.2). All measurements were similar in the control subjects at both visits ( P > 0.05). Endurance training attenuates chemoreflex sensitization to IH, which may partially explain the beneficial effects of exercise training in patients with cardiovascular disease.

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Preejection Period as a Sympathetic Activity Index: a Role of Confounding Factors

Physiological Research ◽

10.33549/physiolres.933682 ◽

2017 ◽

pp. S265-S275 ◽

Cited By ~ 3

Author(s):

J. KROHOVA ◽

B. CZIPPELOVA ◽

Z. TURIANIKOVA ◽

Z. LAZAROVA ◽

I. TONHAJZEROVA ◽

...

Keyword(s):

Blood Pressure ◽

Sympathetic Activity ◽

Mental Stress ◽

Activity Index ◽

Cardiac Contractility ◽

Systolic Time Intervals ◽

Tilt Test ◽

Confounding Factors ◽

Healthy Humans ◽

Arterial Blood

In previous studies, one of the systolic time intervals – preejection period (PEP) – was used as an index of sympathetic activity reflecting the cardiac contractility. However, PEP could be also influenced by several other cardiovascular variables including preload, afterload and diastolic blood pressure (DBP). The aim of this study was to assess the behavior of the PEP together with other potentially confounding cardiovascular system characteristics in healthy humans during mental and orthostatic stress (head-up tilt test – HUT). Forty-nine healthy volunteers (28 females, 21 males, mean age 18.6 years (SD=1.8 years)) participated in the study. We recorded finger arterial blood pressure by volume-clamp method (Finometer Pro, FMS, Netherlands), PEP, thoracic fluid content (TFC) – a measure of preload, and cardiac output (CO) by impedance cardiography (CardioScreen® 2000, Medis, Germany). Systemic vascular resistance (SVR) – a measure of afterload – was calculated as a ratio of mean arterial pressure and CO. We observed that during HUT, an expected decrease in TFC was accompanied by an increase of PEP, an increase of SVR and no significant change in DBP. During mental stress, we observed a decrease of PEP and an increase of TFC, SVR and DBP. Correlating a change in assessed measures (delta values) between mental stress and previous supine rest, we found that ΔPEP correlated negatively with ΔCO and positively with ΔSVR. In orthostasis, no significant correlation between ΔPEP and ΔDBP, ΔTFC, ΔCO, ΔMBP or ΔSVR was found. We conclude that despite an expected increase of sympathetic activity during both challenges, PEP behaved differently indicating an effect of other confounding factors. To interpret PEP values properly, we recommend simultaneously to measure other variables influencing this cardiovascular measure.

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