Daily Exposure to Mild Intermittent Hypoxia Reduces Blood Pressure in Male OSA Patients with Hypertension

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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Hypoxic pressor response, cardiac size, and natriuretic peptides are modified by long-term intermittent hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.6.2025 ◽

1999 ◽

Vol 87 (6) ◽

pp. 2025-2031 ◽

Cited By ~ 30

Author(s):

Holger Kraiczi ◽

Jarkko Magga ◽

Xiang Ying Sun ◽

Heikki Ruskoaho ◽

Xiaohe Zhao ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Body Weight ◽

Atrial Natriuretic Peptide ◽

Right Ventricular ◽

Natriuretic Peptide ◽

Intermittent Hypoxia ◽

Spontaneously Hypertensive ◽

Wistar Kyoto

We investigated whether the effect of long-term intermittent hypoxia (LTIH) on cardiovascular function may be modified by preexisting genetic traits. To induce LTIH experimentally, cycles of 90-s hypoxia (nadir 6%) followed by 90-s normoxia were applied to six Wistar-Kyoto and six spontaneously hypertensive rats during 8 h daily. Comparison with the same number of control animals after 70 days revealed no alteration of intra-arterial blood pressure or heart rate. Blood pressure responsiveness to a brief hypoxic stimulus was enhanced in the LTIH animals, regardless of strain, whereas the hypoxia-induced increase in heart rate was abolished. In the spontaneously hypertensive but not the Wistar-Kyoto rats, LTIH increased left ventricular weight-to-body weight ratio and content of atrial natriuretic peptide mRNA. Expression of B-type natriuretic peptide was unchanged (Northern blot). Slightly increased right ventricular weight-to-body weight ratios in the LTIH animals were associated with higher right ventricular atrial natriuretic peptide and B-type natriuretic peptide mRNA amounts. Consequently, the effects of LTIH on different components of cardiovascular function appear incompletely related to each other and differentially influenced by constitutional traits.

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Short-term intermittent hypoxia enhances sympathetic responses to continuous hypoxia in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00036.2007 ◽

2007 ◽

Vol 103 (3) ◽

pp. 835-842 ◽

Cited By ~ 28

Author(s):

Urs A. Leuenberger ◽

Cynthia S. Hogeman ◽

Sadeq Quraishi ◽

Latoya Linton-Frazier ◽

Kristen S. Gray

Keyword(s):

Blood Pressure ◽

Sleep Apnea ◽

Sympathetic Activity ◽

Intermittent Hypoxia ◽

Muscle Sympathetic Nerve Activity ◽

Acute Hypoxia ◽

Short Term ◽

Healthy Humans ◽

Obstructive Sleep ◽

Normal 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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Effects of Intermittent Hypoxia on Blood Pressure, Serum Plasminogen Activator Inhibitor 1 and Glucose Metabolism in Male Sprague Dawley Rats.

10.1210/endo-meetings.2010.part3.p10.p3-465 ◽

2010 ◽

pp. P3-465-P3-465

Author(s):

LE Aguirre ◽

X DeLeon ◽

KL Sweazea ◽

BR Walker ◽

KM Colleran ◽

...

Keyword(s):

Blood Pressure ◽

Glucose Metabolism ◽

Plasminogen Activator ◽

Intermittent Hypoxia ◽

Plasminogen Activator Inhibitor ◽

Sprague Dawley ◽

Plasminogen Activator Inhibitor 1 ◽

Sprague Dawley Rats ◽

Activator Inhibitor

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Intermittent hypoxia prior to completion of nephrogenesis increases systolic blood pressure and proteinuria after angiotensin II treatment in adult male rats

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.593.6 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Lindsey A Ramirez ◽

Elizabeth Snyder ◽

Terri Marin ◽

Jennifer C Sullivan

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Systolic Blood Pressure ◽

Adult Male ◽

Intermittent Hypoxia ◽

Male Rats

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Crucial Role of the Carotid Body Chemoreceptors on the Development of High Arterial Blood Pressure During Chronic Intermittent Hypoxia

Advances in Experimental Medicine and Biology - Arterial Chemoreceptors in Physiology and Pathophysiology ◽

10.1007/978-3-319-18440-1_29 ◽

2015 ◽

pp. 255-260 ◽

Cited By ~ 7

Author(s):

Rodrigo Iturriaga ◽

David C. Andrade ◽

Rodrigo Del Rio

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Carotid Body ◽

Crucial Role ◽

Intermittent Hypoxia ◽

Chronic Intermittent Hypoxia ◽

Arterial Blood ◽

Carotid Body Chemoreceptors

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Combined intermittent and sustained hypoxia is a novel and deleterious cardio-metabolic phenotype

SLEEP ◽

10.1093/sleep/zsab290 ◽

2021 ◽

Author(s):

Xin Zhen ◽

Esteban A Moya ◽

Mary Gautane ◽

Huayi Zhao ◽

Elijah S Lawrence ◽

...

Keyword(s):

Blood Pressure ◽

Intermittent Hypoxia ◽

Systolic Pressure ◽

Metabolic Effects ◽

Metabolic Phenotype ◽

Glucose Disposal ◽

Chronic Obstructive ◽

Ventricular Systolic Pressure ◽

Obstructive Sleep ◽

Sustained Hypoxia

Abstract Study objectives Chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome is associated with excess mortality, and outcomes are related to the degree of hypoxemia. People at high altitude are susceptible to periodic breathing, and hypoxia at altitude is associated with cardio-metabolic dysfunction. Hypoxemia in these scenarios may be described as superimposed sustained plus intermittent hypoxia, or overlap hypoxia (OH), the effects of which have not been investigated. We aimed to characterize the cardio-metabolic consequences of OH in mice. Methods C57BL/6J mice were subjected to either sustained hypoxia (SH, FiO2=0.10), intermittent hypoxia (IH, FiO2=0.21 for 12 hours, and FiO2 oscillating between 0.21 and 0.06, 60 times/hour, for 12 hours), OH (FiO2=0.13 for 12 hours, and FiO2 oscillating between 0.13 and 0.06, 60 times/hour, for 12 hours), or room air (RA), n=8/group. Blood pressure and intraperitoneal glucose tolerance test were measured serially, and right ventricular systolic pressure (RVSP) was assessed. Results Systolic blood pressure transiently increased in IH and OH relative to SH and RA. RVSP did not increase in IH, but increased in SH and OH by 52% (p<0.001) and 20% (p=0.001). Glucose disposal worsened in IH and improved in SH, with no change in OH. Serum LDL and VLDL increased in OH and SH, but not in IH. Hepatic oxidative stress increased in all hypoxic groups, with the highest increase in OH. Conclusions Overlap hypoxia may represent a unique and deleterious cardio-metabolic stimulus, causing systemic and pulmonary hypertension, and without protective metabolic effects characteristic of sustained hypoxia.

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