Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recurrent episodic hypoxia (EH) is a feature of sleep apnea that may be responsible for some chronic cardiovascular sequelae such as systemic hypertension. Chronic EH (8 h/day for 35 days) causes elevation of diurnal resting (unstimulated) mean arterial blood pressure (MAP) in the rat. We used in vivo video microscopy to examine arteriolar reactivity in the cremaster muscle of male Sprague-Dawley rats subjected to 35 days of EH. Cremaster muscles of EH (n = 6) and control (n = 6) rats were exposed to varying doses of norepinephrine (NE) (10(-10) to 10(-5) M), ACh (10(-9) to 10(-5) M), and endothelin-1 (10(-12) to 10(-8) M). In a separate experiment, EH (n = 5) and control (n = 6) rats were given one dose of a nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-5) M). We also examined endothelial NOS mRNA from the kidneys of EH-stimulated and control (unstimulated) rats. Telemetry-monitored EH rats showed a 16-mmHg increase in MAP over 35 days, whereas control rats showed no change. The response to NE and endothelin-1 were similar for EH and control rats. ACh vasodilatation of arterioles in EH rats was significantly attenuated compared with that of controls. The degree of vasoconstriction in response to blockade of the nitric oxide system by L-NAME was significantly less (83% of baseline diameter with L-NAME) for arterioles of EH rats compared with that for controls (61% of baseline diameter), implying lower basal resting nitric oxide release in the EH rats. Whole kidney mRNA endothelial NOS levels were not different between groups. These data support the hypothesis that chronic elevation of blood pressure associated with EH involves increased peripheral resistance from decreased basal release or production of nitric oxide after 35 days of EH.
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PMID:Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats. 1129 97

Several growth factors (GFs) are implicated in sleep regulation. It is posited that these GFs are produced in response to neural activity and affect input-output relationships within the neural circuits where they are produced, thereby inducing a local state shift. These GFs also influence synaptic efficacy. All the GFs currently identified as sleep regulatory substances are also implicated in synaptic plasticity. Among these substances, the most extensively studied for their role in sleep regulation are interleukin-1beta (IL-1) and tumor necrosis factor alpha (TNF). Injection of IL-1 or TNF enhances non-rapid eye movement sleep (NREMS). Inhibition of either IL-1 or TNF inhibits spontaneous sleep and the sleep rebound that occurs after sleep deprivation. Stimulation of the endogenous production of IL-1 and TNF enhances NREMS. Brain levels of IL-1 and TNF correlate with sleep propensity; for example, after sleep deprivation, their levels increase. IL-1 and TNF are part of a complex biochemical cascade regulating sleep. Downstream events include nitric oxide, growth hormone releasing hormone, nerve growth factor, nuclear factor kappa B, and possibly adenosine and prostaglandins. Endogenous substances moderating the effects of IL-1 and TNF include anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. Clinical conditions altering IL-1 or TNF activity are associated with changes in sleep, for example, infectious disease and sleep apnea. As our knowledge of the biochemical regulation of sleep progresses, our understanding of sleep function and of many clinical conditions will improve.
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PMID:The role of cytokines in physiological sleep regulation. 1200 22

Respiratory disorders are common and important complications in acromegaly. Patients suffering from acromegaly display a 1.6-3.3 fold increase in mortality rate, which is due to respiratory disorders in 25% of cases. In these patients, mortality for lung disease is 2-3 fold higher than in the general population. Every portion of the respiratory system may be involved. Deformities of facial bones, edema and hypertrophy of the mucosae and pharyngeal and laryngeal cartilages, enlargement of the tongue and inspiratory collapse of the hypopharinx, all may contribute to respiratory alterations. Nasal polyps, "hormonal rhinitis", changes of the voice and snoring are common occurrences. Though rarely, a laryngocele may ensue. Pneumomegaly is frequently observed and, as suggested by functional studies, might be due to an increased number rather than volume of the alveoli. An obstructive respiratory syndrome caused by mucosal thickening of the upper airways and bronchi is observed in 25% of female and 70% of male patients. The sleep apnea syndrome (SAS) affects 60-70% of acromegalic patients. SAS may be of obstructive, central or mixed type. Obstructive SAS is the prevailing form in acromegaly. It is due to intermittent obstruction of upper airways with preserved activity of the respiratory center, as testified by the remarkable thoracic and abdominal respiratory efforts. The pathogenesis of the central type of SAS is more complex. Narrowing of the upper airways may induce reflex inhibition of the respiratory center. Moreover, increased GH levels and, possibly, defects in the somatostatinergic pathways, may increase the ventilatory response of the respiratory center to carbon dioxide, thereby leading to respiratory arrest. In the mixed type of SAS, the phenomena underlying the other two forms coexist. Oxygen desaturation concomitant with the apneic episodes accounts for the frequent nocturnal wakening and diurnal drowsiness. Among the clinical correlates of SAS, arterial hypertension is of particular interest due to the close correlation existing between the two disorders. Sleep deprivation related to SAS seems per se to favor the appearance of hypertension. Moreover, short lasting hypoxemia may induce prolonged elevations of blood pressure, mediated by decreased endothelial generation of nitric oxide. Thus, since cardiovascular events are the main cause of mortality in patients with acromegaly, it is reasonable to hypothesize that SAS is involved in the reduced life span of these patients.
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PMID:Prevalence and pathogenesis of sleep apnea and lung disease in acromegaly. 1250 76

The obesity epidemic is driving metabolic (insulin resistance) syndrome-related health problems including an approximately threefold increased coronary heart disease risk. Sympathetic hyperfunction may participate in the pathogenesis and complications of the metabolic syndrome including higher blood pressure, a more active renin-angiotensin system, insulin resistance, faster heart rates, and excess cardiovascular disease including sudden death. Possible factors augmenting sympathetic activation in the metabolic syndrome include alterations of insulin, leptin, nonesterified fatty acids (NEFAs), cytokines, tri-iodothyronine, eicosanoids, sleep apnea, nitric oxide, endorphins, and neuropeptide Y. Of note, high plasma NEFAs are a risk factor for hypertension and sudden death. In short-term human studies, NEFAs can raise blood pressure, heart rate, and a(1)-adrenoceptor vasoreactivity, while reducing baroreflex sensitivity, endothelium-dependent vasodilatation, and vascular compliance. Efforts to further identify the mechanisms and consequences of sympathetic dysfunction in the metabolic syndrome may provide insights for therapeutic advances to ameliorate the excess cardiovascular risk and adverse outcomes.
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PMID:Insulin resistance and the sympathetic nervous system. 1272 58

Sleep apnea syndrome has been shown to be associated with decreased levels of circulating nitric oxide (NO) after waking up from sleep. In this study we investigated overnight plasma concentrations of NO in sleep apnea patients before and after nasal continuous positive airway pressure (nCPAP) treatment and the effects of nCPAP on morning levels of L-arginine. In experiment 1, NO concentrations measured hourly during sleep were found to be significantly lower in a group of eight sleep apnea patients in comparison with six age-similar snorers and six normal young adults. In experiment 2, overnight NO concentrations were compared in 5 sleep apnea patients before and 9.3 +/- 3.9 mo after treatment with nCPAP. A significant increase in NO concentrations was found in four out of five patients, and a significant increase in L-arginine was found in all five patients after treatment. In experiment 3, removal of nCPAP for a single night in seven sleep apnea patients caused a significant decrease in morning levels of NO and L-arginine. These results demonstrate that sleep apnea is associated with a chronic state of diminished circulating NO concentrations that can be ameliorated by nCPAP treatment.
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PMID:Plasma levels of nitric oxide and L-arginine in sleep apnea patients: effects of nCPAP treatment. 1450 Sep 96

Sleep-related breathing disorders (SBAS) affect approximately 8% of the population of middle aged adults. At the age of 20 years, approximately 10% of the population snore, while at the age of 60 about 50% of men snore. Some 9% of middle aged women and 24% of middle aged men have an apnea hypopnea index (AHI) of >5 (number of nocturnal apnea and hypopnea per hour of sleep). Sleep apnea hypopnea syndrome is found in 2% of the women and 4% of the men, i.e. they have an AHI>5 associated with daytime sleepiness. Forms, check lists, summaries and patient-readable questionnaires have proved helpful in the evaluation of SBAS.
HNO 2005 Nov
PMID:[Sleep-related breathing disorders. Sleep anamnesis questionnaire and determination of clinical results within the framework of staged diagnostics]. 1621 11

The insulin resistance syndrome (IRS) is considered to be a new target of risk-reduction therapy. The IRS is a cluster of closely associated and interdependent abnormalities and clinical outcomes that occur more commonly in insulin-resistant/hyperinsulinemic individuals. This syndrome predisposes individuals to type 2 diabetes, cardiovascular diseases, essential hypertension, certain forms of cancer, polycystic ovary syndrome, nonalcoholic fatty liver disease, and sleep apnea. In patients at high risk for cardiovascular diseases, endothelial dysfunction is observed in morphologically intact vessels even before the onset of clinically manifest vascular disease. Indeed, there are several lines of evidence that indicate that endothelial function is compromised in situations where there is reduced sensitivity to endogenous insulin. It is well established that a decreased bioavailability of nitric oxide (NO) contributes to endothelial dysfunction. Furthermore, NO may modulate insulin sensitivity. Activation of NO synthase (NOS) augments blood flow to insulin-sensitive tissues (i.e. skeletal muscle, liver, adipose tissue), and its activity is impaired in insulin resistance. Inhibition of NOS reduces the microvascular delivery of nutrients and blunts insulin-stimulated glucose uptake in skeletal muscle. Furthermore, induction of hypertension by administration of the NOS inhibitor NG-monomethyl-L-arginine is also associated with insulin resistance in rats. Increased levels of asymmetric dimethylarginine (ADMA) are associated with endothelial vasodilator dysfunction and increased risk of cardiovascular diseases. An intriguing relationship exists between insulin resistance and ADMA. Plasma levels of ADMA are positively correlated with insulin resistance in nondiabetic, normotensive people. New basic research insights that provide possible mechanisms underlying the development of insulin resistance in the setting of impaired NO bioavailability will be discussed.
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PMID:Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA. 1644 67

The effects of nitric oxide (NO) are mediated by cyclic guanosine monophosphate (cGMP)-dependent and cGMP-independent processes. Most cGMP-independent effects are mediated by the actions of S-nitrosothiols (SNOs). SNOs have been shown to play a role in health and in disease. In studies performed in the mouse and rat, the ventilatory response to hypoxia is regulated in the nucleus tractus solitarius by SNOs exported from red blood cells. This may affect the treatment of respiratory distress in newborns and sleep apnea in adults. Likewise, SNOs have been shown to alter the stability and abundance of the transcription factor hypoxia inducible factor-1, altering the expression of hypoxia-regulated genes. Identification of the proteins involved in these signaling events will lead to new therapeutic approaches in the treatment of diseases characterized by limited oxygen availability.
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PMID:Regulation of respiration and endothelial gene expression by S-nitrosothiols in health and disease. 1656 26

Breathing is generated and controlled by a brainstem neuronal network. Both intrinsic and synaptic interactions are involved in respiratory rhythm generation and their contribution is state-dependent, changing with hypoxia and the neuromodulatory state. Cellular mechanisms involved in acute or chronic pathological conditions are still unknown. A dysfunction in the neuronal network that controls breathing may be involved in several respiratory disorders such as central sleep apnea, sudden infant death syndrome, congenital hypoventilation, and in some clinical conditions that produce breathing dysfunction such as drug-induced respiratory depression, obesity hypoventilation syndrome, etc. Despite the fact that several drugs are currently used to treat these diseases, the probable effects of this pharmacotherapy on the central rhythm generator and on other neuronal networks related with breathing control is poorly understood. Here, we review the current pharmacological approaches in the treatment of respiratory disorders, such as acetazolamide, theophylline, aminophylline, progesterone, nitric oxide. Possible effects of these drugs on the central respiratory network are discussed and putative therapeutic targets for the development of future pharmacological therapies suggested.
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PMID:Breathing generation and potential pharmacotherapeutic approaches to central respiratory disorders. 1701 19

Sleep apnea associated with chronic intermittent hypoxia (IH) impairs hippocampal functions but the pathogenic mechanisms involving dysfunction of nitric oxide (NO) and ionic channels remain unclear. We examined the hypothesis that hippocampal NO deficit impairs the activity of large conductance calcium-activated potassium (BK) channels in rats with chronic IH, mimicking conditions in patients with sleep apnea. A patch-clamp study was performed on hippocampal CA1 neurons acutely dissociated from IH and control rats. The levels of endogenous NO and intracellular calcium in the CA1 region of the hippocampal slices were measured respectively by electrochemical microsensors and spectrofluorometry. We found that the open probability of BK channels remarkably decreased in the CA1 pyramidal neurons in a time-dependent manner with the IH treatment, without changes in the unitary conductance and reversal potential. NO donors, SNP or DETA/NO, significantly restored the activity of BK channels in the IH neurons, which was prevented by blockade of S-nitrosylation with NEM or MTSES but not by inhibition of the cGMP pathway with ODQ or 8-bromo-cGMP. Endogenous NO levels were substantially lowered in the IH hippocampus during resting and hypoxia. Also, the level of protein expression of neuronal NO synthase was markedly lessened in the IH neurons with decreased intracellular calcium response to hypoxia. Collectively, the results suggest that the IH-induced NO deficit mediated by a down-regulation of the expression of neuronal NO synthase plays a causative role in the impaired activity of BK channels, which could account for the hippocampal injury in patients with sleep apnea.
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PMID:Nitric oxide deficit in chronic intermittent hypoxia impairs large conductance calcium-activated potassium channel activity in rat hippocampal neurons. 1799 5


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