Hypoxia-mediated prolonged elevation of sympathetic nerve activity after periods of intermittent hypoxic apnea

Cutler, Michael J.; Swift, Nicolette Muenter; Keller, David M.; Wasmund, Wendy L.; Smith, Michael L.

doi:10.1152/japplphysiol.00506.2003

Cited by 120 publications

(124 citation statements)

References 27 publications

(41 reference statements)

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“…However, vasoconstriction seen in normoxic conditions is preserved in the setting of hypoxia, with Tyramine infusion leading to increased release of catecholamines (6, 7). Interestingly short-term hypoxic exposure has produced sympathoexcitation with no changes in FVR in several studies (4,21,24,29). It would appear that in the setting of sympathoexcitation following brief hypoxia, vasodilation is most appropriately explained by a change in the balance between sympathoexcitation and local vasodilators favoring vasodilation (25,28).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evidence of impaired hypoxic vasodilation after intermediate-duration hypoxic exposure in humans

Gilmartin¹,

Tamisier²,

Anand³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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-Systemic hemodynamics, including forearm blood flow and ventilatory parameters, were evaluated in 21 subjects before and after exposure to 8 h of poikilocapnic hypoxia. To evaluate the role of sympathetic nervous system activation in the changes, in 10 of these subjects, we measured muscle sympathetic nerve activity (MSNA) before and after exposure, and the remaining 11 subjects received intra-arterial phentolamine infusion in the brachial artery to define vascular tone in the absence of sympathetically mediated vasoconstriction. Short-term ventilatory acclimatization occurred as evidenced by a decrease in resting PCO 2 (from 42 Ϯ 1.4 to 37 Ϯ 0.96 mmHg) and by an increase in the slope of the ventilatory response to acute hypoxia [from 0.7 Ϯ 0.1 to 1.2 Ϯ 0.2 l ⅐ min Ϫ1 ⅐ %SpO 2 (blood O2 saturation from pulse oximetry)] after exposure. Subjects demonstrated a significant increase in resting heart rate (from 61 Ϯ 2 to 65 Ϯ 2 beats/min) and diastolic blood pressure (from 64.8 Ϯ 2.7 to 70.4 Ϯ 2.0 mmHg). MSNA did not change significantly after exposure, although there was a trend toward a decrease in burst frequency (from 19.8 Ϯ 4.1 to 14.3 Ϯ 1.2 bursts/min). Forearm vascular resistance showed a significant decrease after termination of exposure (from 37.7 Ϯ 3.6 to 27.6 Ϯ 2.7 mmHg ⅐ ml Ϫ1 ⅐ min ⅐ 100 g tissue, P Ͻ 0.05). Initially, progressive isocapnic hypoxia elicited significant vasodilation, but after 8 h of poikilocapnic hypoxic exposure, the acute challenge failed to change forearm vascular resistance. Local ␣-blockade with phentolamine restored the vasodilatory response to acute hypoxia in the postexposure setting.acclimatization; muscle sympathetic nerve activity; vascular resistance EXTENDED EXPOSURES TO HYPOXIA are associated with increases in ventilation that persist after termination of the exposure. This increase in ventilation, termed hypoxic acclimatization, is attributed primarily to an increase in peripheral chemosensitivity (2,5). Acclimatization has been demonstrated to occur following exposures as brief as 8 h in human subjects (15,16). Because afferent traffic from the peripheral chemoreceptor partly determines sympathetic activity, we postulated that a hypoxic exposure of sufficient duration to induce ventilatory acclimatization also would induce sustained sympathoexcitation that would persist after termination of the hypoxic exposure. To test this hypothesis, we assessed muscle sympathetic nerve activity (MSNA) in normal volunteers before and after an 8-h exposure to hypoxia previously shown to produce ventilatory acclimatization. Because hypoxic exposure also stimulates release of endogenous vasodilators that may persist after the exposure, we further sought to define vascular tone in our subjects by assessing vascular resistance both with and without local blockade of sympathetic input with the use of nonspecific ␣-blockade with local arterial infusion of phentolamine.The goals of this study, therefore, were 1) to define the changes in MSNA associated with ventilatory acclimatization followi...

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Section: Discussionmentioning

confidence: 99%

“…Both short-and long-term exposure to hypoxia has been shown to contribute to significant sympathoexcitation (3,4,14,21,29). Brief hypoxia shows the presence of sympathoexcitation in the setting of a significant decrease in vascular resistance after termination of the exposure (24).…”

Section: Discussionmentioning

confidence: 99%

Evidence of impaired hypoxic vasodilation after intermediate-duration hypoxic exposure in humans

Gilmartin¹,

Tamisier²,

Anand³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Intermittent hypoxia can affect insulin sensitivity and glucose regulation but it is unknown whether OSA attributes significantly to metabolic syndrome or whether these are more attributable to obesity [79]. Experiments on voluntary apneas have shown acute and lasting effects on autonomic regulation of the cardiovascular system and increased sympathetic nerve activity caused by hypoxia [81,82]. Hypoxia has also been shown to induce hypoxic spreading depression-like depolarization in areas throughout the brain, including hippocampal [83] and cortical tissues [84].…”

Section: Breath-holding and Breathing Disordersmentioning

confidence: 99%

Widespread depolarization during expiration: A source of respiratory drive?

Jerath¹,

Crawford²,

Barnes

et al. 2015

Medical Hypotheses

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a b s t r a c tRespiration influences various pacemakers and rhythms of the body during inspiration and expiration but the underlying mechanisms are relatively unknown. Understanding this phenomenon is important, as breathing disorders, breath holding, and hyperventilation can lead to significant medical conditions. We discuss the physiological modulation of heart rhythm, blood pressure, sympathetic nerve activity, EEG, and other changes observed during inspiration and expiration. We also correlate the intracellular mitochondrial respiratory metabolic processes with real-time breathing and correlate membrane potential changes with inspiration and expiration. We propose that widespread minor hyperpolarization occurs during inspiration and widespread minor depolarization occurs during expiration. This depolarization is likely a source of respiratory drive. Further knowledge of intracellular and extracellular ionic changes associated with respiration will enhance our understanding of respiration and its role as a modulator of cellular membrane potential. This could expand treatment options for a wide range of health conditions, such as breathing disorders, stress-related disorders, and further our understanding of the Hering-Breuer reflex and respiratory sinus arrhythmia.Ó 2014 Elsevier Ltd. All rights reserved. IntroductionIn addition to gas exchange and oxygenation of the blood, respiration in the lungs can regulate multiple physiological processes throughout the body. Studies of the cardiovascular system, the peripheral nervous system, and the central nervous system provide evidence that respiratory patterns can exert a significant and immediate influence on a wide range of bodily functions, including changes in blood pressure and sympathovagal balance. Patterned respiration can regulate blood pressure and heart rate [1], as well as regulate rhythmic centers of the brain that control cardiovascular output [2,3]. While the majority of these findings have demonstrated the impact of respiration on cardiac output and other processes in isolated preparations, little work has focused on respiration's direct influence on membrane potential.This article reviews the current understanding of respiration as a regulator of cardiovascular physiology and nervous system function. More specifically, we discuss the role of respiratory rhythm and rate on both systemic and local control of these systems. We describe the role of pulmonary stretch receptors (with a focus on slowly adapting receptors) in converting breathing patterns into a functional, multi-faceted, mechanism that allows respiration to communicate with, and direct various aspects of cardiovascular and nervous system physiology. We propose a hypothesis in which inspiration and expiration are associated with transient increases and decreases in membrane potential that may underlie these widespread changes and how these membrane potential changes may underlie the chaotic dynamics of rhythmic breathing.Many studies focus on the brainstem as the primary modulator of resp...

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“…However, at recovery after mental stress, muscle SN activity returned promptly to baseline levels while HR remained elevated in heart failure patients compared with control subjects in whom muscle SN activity remained elevated and HR returned promptly to baseline (20). In a study of healthy volunteers, hypoxic stress produced long-lasting SN activation after the withdrawal from the stress, but hypercapnic stress did not produce a sustained elevation of SN activity (6,38). In the present study, however, hypercapnia caused a prolonged elevation of cardiac and renal iNE levels in SS rats in association with a slower reduction in HR after stress; both returned rapidly to baseline after the stress in SR rats.…”

Section: Discussionmentioning

confidence: 91%

“…Sustained increases in SN activity after transient stress may accelerate cardiovascular damage. In studies of healthy volunteers, long-lasting muscle SN activation was evoked after the transient stress induced by hypoxemia (6,38). In another study, an increase in renal vascular resistance during the handgrip exercise was exaggerated and prolonged in patients with heart failure compared with normal subjects (21), whereas earlier recovery of increased SN activity after mental stress has also been reported (20).…”

mentioning

confidence: 95%

Transient hypercapnic stress causes exaggerated and prolonged elevation of cardiac and renal interstitial norepinephrine levels in conscious hypertensive rats

Sobajima

Nozawa

Nakadate

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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The responses of sympathetic nerve activity to transient stress can be exaggerated in salt-sensitive (SS), hypertensive subjects. Cardiac and renal interstitial norepinephrine (iNE) levels during and after transient hypercapnia were investigated in conscious SS rats. Dahl SS and salt-resistant (SR) 6-wk-old rats were fed a high-salt diet, and at 12 wk iNE levels in the heart and kidney were determined using microdialysis with probes inserted in the left ventricular (LV) wall and kidney. A telemetry system determined blood pressure and heart rate (HR) in separate animals. After recovery from the operation, data were collected before, during, and after exposure to normoxic 10% CO 2 for 25 min under unanesthetized conditions. The plasma NE concentrations at baseline did not differ between the two strains. Both cardiac and renal iNE levels were much higher in SS rats than in SR rats at baseline as well as during hypercapnic stress. After stress, the markedly increased iNE levels of SS rats were prolonged in the LV as well as in the kidney. During hypercapnic stress, HR decreased in both SS and SR rats, while sudden increases in HR immediately after the withdrawal from stress were followed by its slower reduction in SS rats compared with SR rats. In conclusion, transient hypercapnic stress causes exaggerated and prolonged elevation of iNE levels in the heart as well as in kidneys of SS animals. salt-sensitive; interstitial norepinephrine; hypercapnia CENTRAL SYMPATHOEXCITATION and renal fluid retention may be involved in the development of salt-sensitive (SS) hypertension. Transient environmental or mental stress in SS animals and subjects causes a greater increase in blood pressure (BP) and renal sympathetic nerve (SN) activity and greater antinatriuresis compared with salt-resistant (SR) animals and subjects (2,3,9,16). Hypertension is also accompanied by increased chemoreflex sensitivity (29, 33) and, therefore, hypoxic and/or hypercapnic stress could augment SN activity in SS hypertensive subjects complicated by sleep apnea syndrome. Thus, the enhanced SN responsiveness to stress may play a role in the high morbidity or mortality of SS hypertensive subjects. However, it remains unclear whether the augmented response of renal SN activity to transient stress occurs in parallel to the response in other organs, especially in the heart, because it is difficult to directly determine cardiac SN activity in conscious animals. Kamiya et al. (11) reported that muscle SN activity parallels the renal and cardiac SN activity in response to baroreceptor pressure changes in anesthetized rabbits. In contrast, others have reported that central or peripheral stimuli cause selective and differential influences on the SN activity of each organ in anesthetized and conscious animals (13,36,37).Previous studies have shown that cardiovascular recovery from stress plays an important role in the pathogenesis of hypertension and is a predictor of overall mortality (1, 5). Sustained increases in SN activity after transient stress may accel...

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Hypoxia-mediated prolonged elevation of sympathetic nerve activity after periods of intermittent hypoxic apnea

Cited by 120 publications

References 27 publications

Evidence of impaired hypoxic vasodilation after intermediate-duration hypoxic exposure in humans

Evidence of impaired hypoxic vasodilation after intermediate-duration hypoxic exposure in humans

Widespread depolarization during expiration: A source of respiratory drive?

Transient hypercapnic stress causes exaggerated and prolonged elevation of cardiac and renal interstitial norepinephrine levels in conscious hypertensive rats

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