Hypertension and obstructive sleep apnea

Phillips, Brian N.; Somers, Virend K.

doi:10.1007/s11906-003-0083-0

Cited by 27 publications

(13 citation statements)

References 84 publications

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“…ET-1 is a major regulator of vascular smooth muscle tone, and recent data from our laboratory and others suggest that augmented ET-1 vasoconstriction contributes to sleep apnea-induced hypertension (16,30,31). ET-1 initiates vasoconstriction through increases in both [Ca 2ϩ ] i and Ca 2ϩ sensitization (1).…”

Section: Discussionmentioning

confidence: 91%

Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKCδ

Allahdadi

Duling²,

Walker³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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We reported previously that simulating sleep apnea by exposing rats to eucapnic intermittent hypoxia (E-IH) causes endothelin-dependent hypertension and increases constrictor sensitivity to endothelin-1 (ET-1). In addition, augmented ET-1-induced constriction in small mesenteric arteries (sMA) is mediated by increased Ca(2+) sensitization independent of Rho-associated kinase. We hypothesized that exposing rats to E-IH augments ET-1-mediated vasoconstriction by increasing protein kinase C (PKC)-dependent Ca(2+) sensitization. In sMA, the nonselective PKC inhibitor GF-109203x (3 microM) significantly inhibited ET-1-stimulated constriction in E-IH arteries but did not affect ET-1-stimulated constriction in sham arteries. Phospholipase C inhibitor U-73122 (1 microM) also inhibited constriction by ET-1 in E-IH but not sham sMA. In contrast, the classical PKC (cPKC) inhibitor Gö-6976 (1 microM) had no effect on ET-1-mediated vasoconstriction in either group, but a PKCdelta-selective inhibitor (rottlerin, 3 microM) significantly decreased ET-1-mediated constriction in E-IH but not in sham sMA. ET-1 increased PKCdelta phosphorylation in E-IH but not sham sMA. In contrast, ET-1 constriction in thoracic aorta from both sham and E-IH rats was inhibited by Gö-6976 but not by rottlerin. These observations support our hypothesis that E-IH exposure significantly increases ET-1-mediated constriction of sMA through PKCdelta activation and modestly augments ET-1 contraction in thoracic aorta through activation of one or more cPKC isoforms. Therefore, upregulation of a PKC pathway may contribute to elevated ET-1-dependent vascular resistance in this model of hypertension.

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Section: Discussionmentioning

confidence: 91%

Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKCδ

Allahdadi

Duling²,

Walker³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Patients with sleep apnea have been found to be at risk for cardiovascular diseases, such as acute coronary syndromes, systemic hypertension, and pulmonary hypertension, and many other physiological and immunological disorders [33][34][35][36][37][38]. Reduced antioxidant capacity in serum of OSA patients has been reported previously [39].…”

Section: Discussionmentioning

confidence: 99%

Lipid peroxides, superoxide dismutase and circulating IL-8 and GCP-2 in patients with severe obstructive sleep apnea: a pilot study

Alzoghaibi

BaHammam

2005

Sleep Breath

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Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality and many other physiological and immunological disorders. An increase in hypoxia due to OSA may cause generation of reactive oxygen species (ROS). ROS are toxic to biomembranes and may lead to peroxidation of lipids. An increase in systemic biomarkers of inflammation and oxidative stress has been found in patients with OSA. The first aim of this study was to test the hypothesis that OSA is linked to increased oxidative stress (lipid peroxidation) and decreased antioxidant defense [superoxide dismutase (SOD)]. The second aim was to measure the serum levels of neutrophil chemokines [interleukin-8 (IL-8)], and granulocyte chemotactic protein-2 (GCP-2) in OSA patients. Twenty five patients with severe OSA and 17 healthy subjects were recruited. IL-8 and GCP-2 were measured in the serum by a specific enzyme immunoassay kit. Oxidative stress level was quantitated by measurement of thiobarbituric acid reactive substances. SOD enzymatic activity was measured by purely chemical system based on NAD(P)H oxidation. Mean SOD and lipid peroxidation concentrations of patients were not significantly different from those of control subjects (0.29+/-0.015 vs 0.31+/-0.01 U/ml and 4.64+/-0.57 vs 4.62+/-0.54 mmol/ml, respectively). Higher concentrations of IL-8 and GCP-2 were found in OSA patients (198.8+/-4.76 vs 180.83+/-3.38 and 383.34+/-46.19 vs 218+/-13.16 pg/ml, respectively, p<0.005). The present study does not support the hypothesis that OSA is linked to increased oxidative stress and decreased antioxidant defense. On the other hand, it suggests that systemic inflammation characterizes OSA patients.

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“…Recent results also suggest that treatment of obstructive sleep apnea syndrome (OSAS) using continuous positive airway pressure therapy (CPAP) reduces blood pressure in hypertensive patients with OSAS (31)(32)(33)(34)(35). The mechanisms underlying the effect of SDB on hypertension are controversial and may involve hypoxia or/and arousal-induced stimulation of sympathetic tone (36)(37)(38). SDB has also been associated with increased angiotensin II levels (39) and ACE plasma activity (40), suggesting synergistic effects of ACE and SDB on hypertension and cardiovascular risk.…”

mentioning

confidence: 99%

Angiotensin-converting Enzyme, Sleep-disordered Breathing, and Hypertension

Lin

Finn²,

Zhang³

et al. 2004

Am J Respir Crit Care Med

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The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism influences ACE activity, cardiovascular risk, blood pressure, and possibly the risk of developing Alzheimer's dementia. We explored the association of the insertion/deletion polymorphism with sleep-disordered breathing (SDB) and hypertension in 1,100 subjects of the Wisconsin Sleep Cohort. The polymorphism did not influence body mass index or the occurrence of SDB, but was dose-dependently associated with blood pressure. Interestingly, SDB and the insertion/deletion polymorphism interacted significantly to modulate blood pressure independently of age, sex, ethnicity, and body mass index. Most specifically, the association of the deletion allele with hypertension was most pronounced in subjects with mild to moderate degrees of sleep apnea (5 < or = apnea-hypopnea index < or = 30). We hypothesize that in the absence of SDB the effect of the deletion allele alone may not be sufficient to increase blood pressure. At severe levels of SDB, the effect of sleep apnea on blood pressure overwhelms any association of the deletion allele with hypertension and occurs independent of any ACE gene genotype.

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Hypertension and obstructive sleep apnea

Cited by 27 publications

References 84 publications

Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKCδ

Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKCδ

Lipid peroxides, superoxide dismutase and circulating IL-8 and GCP-2 in patients with severe obstructive sleep apnea: a pilot study

Angiotensin-converting Enzyme, Sleep-disordered Breathing, and Hypertension

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