Sleep-disordered Breathing and Cardiovascular Disease

Shahar, Eyal; Cw, Whitney; Redline, Susan; Et, Lee; Newman, Anne; Fj, Nieto; Gt, O'Connor; Ll, Boland; Je, Schwartz; Jm, Samet

doi:10.1164/ajrccm.163.1.2001008

Cited by 2,527 publications

(460 citation statements)

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“…However, cardiorespiratory systems adapt to chronic SH to maintain adequate oxygen delivery to tissues (reviewed in refs. 2 and 3), whereas chronic intermittent hypoxia (CIH) leads to serious pathophysiological consequences such as hypertension, myocardial infarcts, and even stroke (4,5).…”

mentioning

confidence: 99%

Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: Implications for recurrent apneas

Peng

Overholt

Kline

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

406

633

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Reflexes from the carotid body have been implicated in cardiorespiratory disorders associated with chronic intermittent hypoxia (CIH). To investigate whether CIH causes functional and͞or structural plasticity in the carotid body, rats were subjected to 10 days of recurrent hypoxia or normoxia. Acute exposures to 10 episodes of hypoxia evoked long-term facilitation (LTF) of carotid body sensory activity in CIH-conditioned but not in control animals. The magnitude of sensory LTF depended on the length of CIH conditioning and was completely reversible and unique to CIH, because conditioning with a comparable duration of sustained hypoxia was ineffective. Histological analysis revealed no differences in carotid body morphology between control and CIH animals. Previous treatment with superoxide anion (O 2•؊ ) scavenger prevented sensory LTF. In the CIH-conditioned animals, carotid body aconitase enzyme activity decreased compared with controls. These observations suggest that increased generation of reactive oxygen species contribute to sensory LTF. In CIH animals, carotid body complex I activity of the mitochondrial electron transport is inhibited, suggesting mitochondria as one source of O 2•؊ generation. These observations demonstrate that CIH induces a previously uncharacterized form of reactive oxygen species-dependent, reversible, functional plasticity in carotid body sensory activity. The sensory LTF may contribute to persistent reflex activation of sympathetic nerve activity and blood pressure in recurrent apnea patients experiencing CIH.H ypoxia is a pervasive physiological stimulus. Changes in arterial blood oxygen levels are monitored continuously by peripheral chemoreceptors, especially the carotid bodies (reviewed in ref. 1). The ensuing reflexes are critical for maintaining homeostasis during hypoxia. Hypoxia is encountered under many different circumstances. For instance, sojourn to high altitude exposes individuals to sustained hypoxia (SH). On the other hand, people living at sea level experience intermittent hypoxia more often in life than SH. Many pathophysiological situations including recurrent apnea syndromes (central or obstructive sleep apneas), apneas in premature infants, and asthmatic attacks are associated with intermittent hypoxia. Decreases in arterial blood oxygen occur in both types of hypoxia. However, cardiorespiratory systems adapt to chronic SH to maintain adequate oxygen delivery to tissues (reviewed in refs. 2 and 3), whereas chronic intermittent hypoxia (CIH) leads to serious pathophysiological consequences such as hypertension, myocardial infarcts, and even stroke (4, 5).Reflexes from the carotid body have been proposed to play a critical role in ventilatory and circulatory adaptations to chronic SH and are associated with structural changes in the carotid body including hypertrophy of the organ, increased vascularization, and increased number of glomus cells (the putative oxygensensing cells; reviewed in refs. 2 and 3). There is evidence that reflexes arising from the carotid ...

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mentioning

confidence: 99%

Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: Implications for recurrent apneas

Peng

Overholt

Kline

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

406

633

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“…Recurrent apneas are characterized by transient, repetitive cessations of breathing (Ϸ10 sec in adults) resulting in periodic decreases in arterial blood O 2 or intermittent hypoxia (IH). Patients with recurrent apneas are at risk for developing several comorbidities including hypertension, sympathetic activation, breathing abnormalities, atherosclerosis, and stroke (4)(5)(6)(7)(8). Exposure of rodents to IH alone induces several co-morbidities reported in patients with recurrent apnea (9)(10)(11).…”

mentioning

confidence: 99%

Intermittent hypoxia degrades HIF-2α via calpains resulting in oxidative stress: Implications for recurrent apnea-induced morbidities

Nanduri

Wang

Yuan

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

160

227

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Intermittent hypoxia (IH) occurs in many pathological conditions including recurrent apneas. Hypoxia-inducible factors (HIFs) 1 and 2 mediate transcriptional responses to low O 2 . A previous study showed that HIF-1 mediates some of the IH-evoked physiological responses. Because HIF-2␣ is an orthologue of HIF-1␣, we examined the effects of IH on HIF-2␣, the O2-regulated subunit expression, in pheochromocytoma 12 cell cultures. In contrast to the up-regulation of HIF-1␣, HIF-2␣ was down-regulated by IH. Similar down-regulation of HIF-2␣ was also seen in carotid bodies and adrenal medullae from IH-exposed rats. Inhibitors of calpain proteases (ALLM, ALLN) prevented IH-evoked degradation of HIF-2␣ whereas inhibitors of prolyl hydroxylases or proteosome were ineffective. IH activated calpain proteases and down-regulated the endogenous calpain inhibitor calpastatin. IH-evoked HIF-2␣ degradation led to inhibition of SOD2 transcription, resulting in oxidative stress. Over-expression of transcriptionally active HIF-2␣ prevented IH-evoked oxidative stress and restored SOD2 activity. Systemic treatment of IH-exposed rats with ALLM rescued HIF-2␣ degradation and restored SOD2 activity, thereby preventing oxidative stress and hypertension. These observations demonstrate that, unlike continuous hypoxia, IH leads to down-regulation of HIF-2␣ via a calpain-dependent signaling pathway and results in oxidative stress as well as autonomic morbidities.calcium signaling ͉ hypoxia inducible factors S leep-disordered breathing with recurrent apneas is a leading cause of morbidity and mortality affecting an estimated 18 million people in the United States alone (1-4). Recurrent apneas are characterized by transient, repetitive cessations of breathing (Ϸ10 sec in adults) resulting in periodic decreases in arterial blood O 2 or intermittent hypoxia (IH). Patients with recurrent apneas are at risk for developing several comorbidities including hypertension, sympathetic activation, breathing abnormalities, atherosclerosis, and stroke (4-8). Exposure of rodents to IH alone induces several co-morbidities reported in patients with recurrent apnea (9-11). However, little information is available on the molecular mechanisms underlying the morbidities associated with IH.Hypoxia-inducible factors (HIFs) mediate transcriptional responses to low O 2 (12). HIF-1 is the prototypical member of the HIF family and comprises an O 2 -regulated ␣ subunit and a constitutive ␤ subunit (13). HIF-1 transcriptional activity is induced under continuous hypoxia (CH) as a result of HIF-1␣ protein accumulation resulting from decreased O 2 -dependent proline hydroxylation, ubiquitination, and proteasomal degradation (14). Recent studies showed that IH leads to HIF-1␣ accumulation and utilizes signaling pathways distinct from those identified with CH (15). The importance of HIF-1 to IHassociated physiological and pathophysiological responses was studied in mice with heterozygous deficiency of HIF-1␣. IHevoked cardio-respiratory and metabolic morbidities were absent ...

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“…Estudos mostram que a terapia regular com CPAP por no mínimo 5 horas por noite em pacientes com SAOS resulta em benefício na redução dos níveis tensionais tanto sistólicos como diastólicos. O estudo Sleep Heart Health mostrou que pacientes com SAOS (com IAH > 11/hora) tem um risco 2,38 vezes maior para desenvolver insuficiência cardíaca, independentemente de outros fatores de risco 35 .…”

Section: Hipertensão Arterial Sistêmicaunclassified

Síndrome da Apneia Obstrutiva do Sono e Doenças Cardiovasculares

Campostrini

Prado

2014

RNC

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RESUMOIntrodução. A Síndrome da Apneia Obstrutiva do Sono (SAOS) é caracterizada por obstrução parcial ou completa da via aérea superior, de forma intermitente e recorrente durante o sono. As principais manifestações durante o sono incluem roncos, pausas respiratórias, fragmentação do sono, levando a prejuízos diurnos incapacitantes, como sonolência excessiva diurna, alterações cognitivas e cefaléia matinal. Além das manifestações respiratórias clássicas, resulta em alterações metabólicas e hemodinâmicas que predispõem ao desenvolvimento e agravamento de doenças cardiovasculares, tais como hipertensão arterial sistêmica, insuficiência cardíaca congestiva, doença arterial coronariana e arritmias. Objetivo. Abordar aspectos clínicos, fisiopatológicos e diagnósticos da SAOS, bem como seus efeitos deletérios no sistema cardiovascular. Método. Revisão da literatura acerca da SAOS e suas consequências cardiovasculares através de artigos selecionados no PubMed. Conclusão. A apneia obstrutiva do sono e as doenças cardiovasculares têm origem multifatorial e alta prevalência na população mundial. Considerando que as doenças cardiovasculares são a maior causa atual de morbidade e mortalidade no mundo, a determinação de fatores de risco possíveis de controle e tratamento, como a SAOS, torna-se fundamental para prevenção e tratamento das doenças cardiovasculares.Unitermos. Síndrome da Apneia Obstrutiva do Sono, Doenças Cardiovasculares, Hipertensão, insuficiência Cardíaca Congestiva, Doença da Artéria Coronariana, Arritmias Cardíacas.Citação. Campostrini DDA, Prado LBF, Prado GF. Síndrome da Apneia Obstrutiva do Sono e Doenças Cardiovasculares. ABSTRACTIntroduction. Obstructive Sleep Apnea Syndrome (OSAS) is characterized by partial or complete obstruction of the upper airway, intermittently and recurrently during sleep. The main manifestations during sleep include snoring, pauses in breathing, sleep fragmentation, resulting in excessive daytime sleepiness, cognitive dysfunction and morning headaches. Besides the classic respiratory symptoms, OSAS results in metabolic and hemodynamic alterations that predispose to the development and worsening of cardiovascular diseases such as hypertension, congestive heart failure, coronary artery disease and arrhythmias. Objective. Reporting clinical, pathophysiological and diagnostic aspects of OSAS and its deleterious effects on the cardiovascular system. Method. Review of literature about OSAS and its cardiovascular consequences through selected articles in PubMed. Conclusion. Obstructive sleep apnea and cardiovascular diseases have multifactorial origin and high prevalence in the global population. Because cardiovascular diseases are the main cause of the current morbidity and mortality worldwide, determining possible treatable risk factors, such as OSAS, it is fundamental to prevention and treatment of cardiovascular diseases.

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Sleep-disordered Breathing and Cardiovascular Disease

Cited by 2,527 publications

References 37 publications

Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: Implications for recurrent apneas

Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: Implications for recurrent apneas

Intermittent hypoxia degrades HIF-2α via calpains resulting in oxidative stress: Implications for recurrent apnea-induced morbidities

Síndrome da Apneia Obstrutiva do Sono e Doenças Cardiovasculares

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