A Specific and Potent Pressor Effect of Hypoxia in Patients with Sleep Apnea

Hedner, Jan; Wilcox, Ian; Laks, Leon; Grunstein, Ron; Sullivan, Colin E.

doi:10.1164/ajrccm/146.5_pt_1.1240

Cited by 148 publications

(62 citation statements)

References 7 publications

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“…They include 1) recurrent hypoxemia, associated mild hypercapnea, and increased chemoreceptor firing, all of which lead to increased MSNA and increased arterial BP (23,24), 2) arousals during sleep, which directly activate the sympathetic nervous system causing a pressor response (25,26), and 3) recurrent hypoxemia, which triggers endothelial dysfunction leading to impairment of arterial and venous vasodilation (27)(28)(29)(30)(31). Nevertheless, not all patients with OSAS are hypertensive, indicating heterogeneity of BP responses to apnea and sleep fragmentation and the possible intervention of other factors.…”

Section: Discussionmentioning

confidence: 99%

Abnormal Blood Pressure in Prepubertal Children with Sleep-Disordered Breathing

et al. 2004

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The purpose of this study was to investigate the association between low blood pressure (BP) with mild symptoms of orthostatism, sleep-disordered breathing (SDB) and tilt test results in 7-to 12-y-old children. A retrospective chart review of 301 children, ages 7 to 12 y, was initially performed to evaluate the frequency of abnormal BP measurements. Then a prospective study was performed on 7-to 12-y-old prepubertal children with SDB, looking for both abnormal BP and mild orthostatism. All children had polysomnography. Those identified with abnormal (high or low) BP measurements (called "BP outliers") were studied with a new polysomnogram followed by a head-up tilt test as an indicator of autonomic activity. Four of the children with low BP were treated with nasal continuous positive airway pressure and received a second head-up tilt test 3.5 to 7 mo after starting treatment. The prospective study included 78 children, eight of whom were BP outliers. Seven of these outliers had low BP. Compared with all of the SDB subjects, SDB subjects with low BP and indicators of mild orthostatic hypotension had a significantly higher incidence of craniofacial dysmorphism, symptoms of SDB early in life, chronically cold extremities, and dizziness on standing up ( 2 , p ϭ 0.01 to 0.0001). They had a significantly greater drop in BP without evidence of autonomic neuropathy than all other children on head-up tilt testing (Kruskal-Wallis ANOVA with Bonferroni adjustment, p ϭ 0.001 to 0.0001). However, the normotensive SDB controls also had significantly different BP drops than the normal controls (p ϭ 0.0001). The four children placed on nasal continuous positive airway pressure had a nonsignificant trend toward normalization of tilt test response. SDB in prepubertal children can lead to different abnormal stimulation of the autonomic nervous system, with different impacts on BP. The severity and frequency of oxygen saturation drops during sleep, nonhypoxic increases in respiratory effort, and the duration of abnormal breathing are suspected of playing a role in the difference in autonomic nervous system stimulation. In the early 1990s, clinical evaluations of adults with suspected SDB revealed LBP and signs of orthostatic intolerance. A large-scale study was performed thereafter (1). We concurrently investigated whether a similar association could be found in prepubertal children through a retrospective study, briefly summarized later.Because of the limitations of a retrospective study, a prospective study was planned on newly recruited children, taking into account the retrospective results. The prospective study was aimed at a further investigation of possible abnormal autonomic control in children with hypertension and with LBP and mild symptoms of orthostatic intolerance. A head-up tilt test was planned for 1) hypertensive and LBP Tanner stage 1 (2) children, 7 y and older, with symptoms of orthostatic intolerance and SDB; 2) age, ethnicity, sex, and SDB-matched children with normal systolic and diastolic BP and no clinical ...

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Section: Discussionmentioning

confidence: 99%

Abnormal Blood Pressure in Prepubertal Children with Sleep-Disordered Breathing

et al. 2004

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“…For example, compared with control subjects, patients with OSA have an augmented pressor response to hypoxia. 54 Compromised endothelially mediated vasodilation in the setting of increased sympathetic vasoconstrictor discharge would predispose patients with OSA to the development of hypertension. 18,55,56 Hypoxia has been shown to stimulate production of angiogenic substances like vascular endothelial growth factor (VEGF).…”

Section: Bradley and Florasmentioning

confidence: 99%

Sleep Apnea and Heart Failure

2003

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“…Third, even asymptomatic obese individuals have a high incidence of occult obstructive sleep apnea, 26 which may itself be accompanied by abnormalities in chemoreflex function. 27,28 Thus, undiagnosed sleep apnea in apparently normal obese subjects may obscure any distinctive chemoreflex abnormalities associated with obesity per se.We tested the hypothesis that chemoreflex function is altered in obesity, independent of such factors as age, gender, …”

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confidence: 99%

Human Obesity Is Characterized by a Selective Potentiation of Central Chemoreflex Sensitivity

et al. 1999

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Abstract-The chemoreflexes are an important mechanism for regulation of both breathing and autonomic cardiovascular function. Obesity is associated with an increased risk of alveolar hypoventilation and carbon dioxide retention, suggesting that abnormalities in chemoreflex control mechanisms may be implicated. We tested the hypothesis that chemoreflex function is altered in obesity. We compared ventilatory, sympathetic, heart rate, and blood pressure responses to hypercapnia, hypoxia, and the cold pressor test in 14 obese subjects and 14 normal-weight subjects matched for age and gender. During hypercapnia, the increase in minute ventilation was significantly greater in obese subjects (7.0Ϯ0.3 L/min) than in normal-weight subjects (3.3Ϯ1.1 L/min; Pϭ0.03). Despite higher minute ventilation during hypercapnia in obese subjects, the increase in muscle sympathetic nerve activity was similar in obese and normal-weight subjects. When the inhibitory influence of breathing during hypercapnia was eliminated by apnea, the increase in sympathetic nerve activity in obese subjects (99Ϯ16%) was greater than in normal-weight subjects (44Ϯ16%; Pϭ0.02).The magnitude of the ventilatory and autonomic responses to hypoxia and the cold pressor test was similar in obese and normal-weight subjects. We conclude that chemoreflex responses to hypercapnia are potentiated in eucapnic obese subjects. In contrast, responses to hypoxia and to the excitatory cold pressor stimulus in obese subjects are similar to those in normal-weight subjects. Thus, obesity is characterized by selective potentiation of central chemoreflex sensitivity. (Hypertension. 1999;33:1153-1158.)Key Words: hypercapnia Ⅲ hypoxia Ⅲ chemoreceptors Ⅲ sympathetic nervous system Ⅲ obesity T he chemoreflexes are the dominant control mechanisms regulating ventilatory responses to changes in arterial oxygen and CO 2 content. 1-4 Peripheral chemoreceptors, located in the carotid bodies, respond primarily to hypoxia. 1,2 Central chemoreceptors, located on the ventral surface of the medulla, respond primarily to hypercapnia. 3 Both chemoreceptor mechanisms also exert a powerful influence on neural circulatory control. [5][6][7][8] Central and peripheral chemoreflex activation elicit increases in ventilation and sympathetic nerve traffic. 8,9 Increased minute ventilation (V E) inhibits the sympathetic response to chemoreflex activation. 9,10 Obesity is associated with an increased risk of alveolar hypoventilation and CO 2 retention, 11,12 suggesting that chemoreflex control mechanisms may be disturbed. Surprisingly, the effect of obesity on chemoreflex function has received relatively little attention. Previous studies examining chemoreflex function in obese subjects have examined primarily the ventilatory responses. These studies have reported conflicting results, showing either increased, 13,14 decreased, 15 or normal 16,17 responsiveness to hypoxia in obese subjects. Conflicting results have also been reported in studies examining responses to hypercapnia. Obese subjects have bee...

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A Specific and Potent Pressor Effect of Hypoxia in Patients with Sleep Apnea

Cited by 148 publications

References 7 publications

Abnormal Blood Pressure in Prepubertal Children with Sleep-Disordered Breathing

Abnormal Blood Pressure in Prepubertal Children with Sleep-Disordered Breathing

Sleep Apnea and Heart Failure

Human Obesity Is Characterized by a Selective Potentiation of Central Chemoreflex Sensitivity

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