Translational approaches to understanding metabolic dysfunction and cardiovascular consequences of obstructive sleep apnea

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 309, Issue 7, 2015, Pages H1101-H1111

  Drager, Luciano F ^a   Polotsky, Vsevolod Y ^b   O’Donnell, Christopher P ^c   Cravo, Sergio L ^d   Lorenzi Filho, Geraldo ^a   Machado, Benedito H ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d FEDERAL UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

Cardiovascular disease; Intermittent hypoxia; Sleep apnea; Translational medicine

Indexed keywords

ARTICLE; ATHEROSCLEROSIS; AUTONOMIC DYSFUNCTION; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL (TOPIC); DYSLIPIDEMIA; HEART INFARCTION; HUMAN; HYPERTENSION; INFLAMMATION; INSULIN RESISTANCE; LIPID METABOLISM; METABOLIC DISORDER; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; PRIORITY JOURNAL; SLEEP DISORDERED BREATHING; TRANSLATIONAL RESEARCH; ANIMAL; ANOXIA; AUTONOMIC NEUROPATHY; COMPLICATION; DISEASE MODEL; GLUCOSE BLOOD LEVEL; METABOLISM; POSITIVE END EXPIRATORY PRESSURE; PROCEDURES; SLEEP APNEA, OBSTRUCTIVE;

GLUCOSE; GLUCOSE BLOOD LEVEL;

ANIMALS; ANOXIA; AUTONOMIC NERVOUS SYSTEM DISEASES; BLOOD GLUCOSE; CARDIOVASCULAR DISEASES; CONTINUOUS POSITIVE AIRWAY PRESSURE; DIABETES MELLITUS, TYPE 2; DISEASE MODELS, ANIMAL; GLUCOSE; HUMANS; HYPERTENSION; INFLAMMATION; INSULIN RESISTANCE; LIPID METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE; SLEEP APNEA, OBSTRUCTIVE;

EID: 84943193727     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00094.2015     Document Type: Article

References (152)

1. Almado CE, Leao RM, Machado BH. Intrinsic properties of rostral ventrolateral medulla presympathetic and bulbospinal respiratory neurons of juvenile rats are not affected by chronic intermittent hypoxia. Exp Physiol 99: 937-950, 2014.
2. Angheben JM, Schoorlemmer GH, Rossi MV, Silva TA, Cravo SL. Cardiovascular responses induced by obstructive apnea are enhanced in hypertensive rats due to enhanced chemoreceptor responsivity. PLoS One 9: e86868, 2014.
3. Bao G, Metreveli N, Li R, Taylor A, Fletcher EC. Blood pressure response to chronic episodic hypoxia: role of the sympathetic nervous system. J Appl Physiol 83: 95-101, 1997.
4. Barceló A, Piérola J, de la Peña M, Esquinas C, Fuster A, Sanchezde-la-Torre M, Carrera M, Alonso-Fernandez A, Ladaria A, Bosch M, Barbé F. Free fatty acids and the metabolic syndrome in patients with obstructive sleep apnoea. Eur Respir J 37: 1418-1423, 2011.
5. Botros N, Concato J, Mohsenin V, Selim B, Doctor K, Yaggi HK. Obstructive sleep apnea as a risk factor for type 2 diabetes. Am J Med 122: 1122-1127, 2009.
6. Brennick MJ, Pack AI, Ko K, Kim E, Pickup S, Maislin G, Schwab RJ. Altered upper airway and soft tissue structures in the New Zealand Obese mouse. Am J Respir Crit Care Med 179: 158-169, 2009.
7. Brooks D, Horner RL, Kozar LF, Render-Teixeira CL, Phillipson EA. Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. J Clin Invest 99: 106-109, 1997.
8. Brooks B, Cistulli PA, Borkman M, Ross G, McGhee S, Grunstein RR, Sullivan CE, Yue DK. Obstructive sleep apnea in obese noninsulindependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness. J Clin Endocrinol Metab 79: 1681-1685, 1994.
9. Campen MJ, Shimoda LA, O'Donnell CP. Acute and chronic cardiovascular effects of intermittent hypoxia in C57BL/6J mice. J Appl Physiol 99: 2028-2035, 2005.
10. Campos-Rodriguez F, Martinez-Garcia MA, de la Cruz-Moron I, Almeida-Gonzalez C, Catalan-Serra P, Montserrat JM. Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study. Ann Intern Med 156: 115-122, 2012.
11. Campos-Rodriguez F, Martinez-Garcia MA, Reyes-Nuñez N, Caballero-Martinez I, Catalan-Serra P, Almeida-Gonzalez CV. Role of sleep apnea and continuous positive airway pressure therapy in the incidence of stroke or coronary heart disease in women. Am J Respir Crit Care Med 189: 1544-1550, 2014.
12. Carley DW, Berecek K, Videnovic A, Radulovacki M. Sleep-disordered respiration in phenotypically normotensive, genetically hypertensive rats. Am J Respir Crit Care Med 162: 1474-1479, 2000.
13. Chin K, Nakamura T, Shimizu K, Mishima M, Nakamura T, Miyasaka M, Ohi M. Effects of nasal continuous positive airway pressure on soluble cell adhesion molecules in patients with obstructive sleep apnea syndrome. Am J Med 109: 562-567, 2000.
14. Chirinos JA, Gurubhagavatula I, Teff K, Rader DJ, Wadden TA, Townsend R, Foster GD, Maislin G, Saif H, Broderick P, Chittams J, Hanlon AL, Pack AI. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med 370: 2265-2275, 2014.
15. Christon J, Carley DW, Monti D, Radulovacki M. Effects of inspired gas on sleep-related apnea in the rat. J Appl Physiol 80: 2102-2107, 1996.
16. Costa LE, Uchôa CH, Harmon RR, Bortolotto LA, Lorenzi-Filho G, Drager LF. Potential underdiagnosis of obstructive sleep apnoea in the cardiology outpatient setting. Heart 101: 1288-1292, 2015.
17. Danzi-Soares NJ, Genta PR, Nerbass FB, Pedrosa RP, Soares FS, César LA, Drager LF, Skomro R, Lorenzi-Filho G. Obstructive sleep apnea is common among patients referred for coronary artery bypass grafting and can be diagnosed by portable monitoring. Coron Artery Dis 23: 31-38, 2012.
18. Davis EM, Locke LW, McDowell AL, Strollo PJ, O'Donnell CP. Obesity accentuates circadian variability in breathing during sleep in mice but does not predispose to apnea. J Appl Physiol 115: 474-482, 2013.
19. Del Rio R, Moya EA, Iturriaga R. Carotid body and cardiorespiratory alterations in intermittent hypoxia: the oxidative link. Eur Respir J 36: 143-150, 2010.
20. Dempsey JA, Veasey SC, Morgan BJ, O'Donnell CP. Pathophisiology of sleep apnea. Physiol Rev 90: 47-112, 2010.
21. Drager LF, Bortolotto LA, Lorenzi MC, Figueiredo AC, Krieger EM, Lorenzi-Filho G. Early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 172: 613-618, 2005.
22. Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF. Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 176: 706-712, 2007.
23. Drager LF, Bortolotto LA, Figueiredo AC, Silva BC, Krieger EM, Lorenzi-Filho G. Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling. Chest 131: 1379-1386, 2007.
24. Drager LF, Bortolotto LA, Maki-Nunes C, Trombetta IC, Alves MJ, Fraga RF, Negrao CE, Krieger EM, Lorenzi-Filho G. The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome. Atherosclerosis 208: 490-495, 2010.
25. Drager LF, Bortolotto LA, Krieger EM, Lorenzi-Filho G. Additive effects of obstructive sleep apnea and hypertension on early markers of carotid atherosclerosis. Hypertension 53: 64-69, 2009.
26. Drager LF, Genta PR, Pedrosa RP, Nerbass FB, Gonzaga CC, Krieger EM, Lorenzi-Filho G. Characteristics and predictors of obstructive sleep apnea in patients with systemic hypertension. Am J Cardiol 105: 1135-1139, 2010.
27. Drager LF, Lopes HF, Maki-Nunes C, Trombetta IC, Toschi-Dias E, Alves MJ, Fraga RF, Jun JC, Negrão CE, Krieger EM, Polotsky VY, Lorenzi-Filho G. The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome. PLoS One 5: e12065, 2010.
28. Drager LF, Li J, Reinke C, Bevans-Fonti S, Jun JC, Polotsky VY. Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity. Obesity (Silver Spring) 19: 2167-2174, 2011.
29. Drager LF, Li J, Shin MK, Reinke C, Aggarwal NR, Jun JC, Bevans-Fonti S, Sztalryd C, O'Byrne SM, Kroupa O, Olivecrona G, Blaner WS, Polotsky VY. Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea. Eur Heart J 33: 783-790, 2012.
30. Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol 62: 569-576, 2013.
31. Drager LF, Yao Q, Hernandez KL, Shin MK, Bevans-Fonti S, Gay J, Sussan TE, Jun JC, Myers AC, Olivecrona G, Schwartz AR, Halberg N, Scherer PE, Semenza GL, Powell DR, Polotsky VY. Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4. Am J Respir Crit Care Med 188: 240-248, 2013.
32. Dyugovskaya L, Lavie P, Lavie L. Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 165: 934-939, 2002.
33. Fang G, Song D, Ye X, Mao SZ, Liu G, Liu SF. Chronic intermittenthypoxia exposure induces atherosclerosis in ApoE knockout mice: role of NF-κB p50. Am J Pathol 181: 1530-1539, 2012.
34. Farré R, Nacher M, Serrano-Mollar A, Galdiz JB, Alvarez FJ, Navajas D, Montserrat JM. Rat model of chronic recurrent airway obstructions to study the sleep apnea syndrome. Sleep 30: 930-933, 2007.
35. Fatouleh R, McKenzie DK, Macefield VG. Respiratory modulation of muscle sympathetic nerve activity in obstructive sleep apnoea. Exp Physiol 99: 1288-1298, 2014.
36. Fletcher EC, Lesske J, Qian W, Miller CC, 3rd, Unger T. Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats. Hypertension 19: 555-561, 1992.
37. Fletcher EC, Bao G, Miller CC 3rd. Effect of recurrent episodic hypocapnic, eucapnic, and hypercapnic hypoxia on systemic blood pressure. J Appl Physiol 78: 1516-1521, 1995.
38. Fletcher EC. An animal model of the relationship between systemic hypertension and repetitive episodic hypoxia as seen in sleep apnoea. J Sleep Res 4: 71-77, 1995.
39. Foster GE, Poulin MJ, Hanly PJ. Intermittent hypoxia and vascular function: implications forobstructive sleep apnoea. Exp Physiol 92: 51-65, 2007.
40. Foster GD, Sanders MH, Millman R, Zammit G, Borradaile KE, Newman AB, Wadden TA, Kelley D, Wing RR, Sunyer FX, Darcey V, Kuna ST; Sleep AHEAD. Research Group. Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Care 32: 1017-1019, 2009.
41. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA 300: 2142-2152, 2008.
42. Friedman L, Haines A, Klann K, Gallaugher L, Salibra L, Han F, Strohl KP. Ventilatory behavior during sleep among A/J and C57BL/6J mouse strains. J Appl Physiol 97: 1787-1795, 2004.
43. Gami AS, Pressman G, Caples SM, Kanagala R, Gard JJ, Davison DE, Malouf JF, Ammash NM, Friedman PA, Somers VK. Association of atrial fibrillation and obstructive sleep apnea. Circulation 110: 364-367, 2004.
44. Garcia-Rio F, Alonso-Fernández A, Armada E, Mediano O, Lores V, Rojo B, Fernández-Lahera J, Fernández-Navarro I, Carpio C, Ramírez T. CPAP effect on recurrent episodes in patients with sleep apnea and myocardial infarction. Int J Cardiol 168: 1328-1335, 2013.
45. Ge X, Han F, Huang Y, Zhang Y, Yang T, Bai C, Guo X. Is obstructive sleep apnea associated with cardiovascular and all-cause mortality? PLoS One 8: e69432, 2013.
46. Geovanini GR, Gowdak LH, Pereira AC, Danzi-SoaresNde J, Dourado LO, Poppi NT, Cesar LA, Drager LF, Lorenzi-Filho G. OSA and depression are common and independently associated with refractory angina in patients with coronary artery disease. Chest 146: 73-80, 2014.
47. Hamrahi H, Chan B, Horner RL. On-line detection of sleep-wake states and application to produce intermittent hypoxia only in sleep in rats. J Appl Physiol 90: 2130-2140, 2001.
48. Han F, Subramanian S, Price ER, Nadeau J, Strohl KP. Periodic breathing in the mouse. J Appl Physiol 92: 1133-1140, 2002.
49. Hendricks JC, Kline LR, Kovalski RJ, O'Brien JA, Morrison AR, Pack AI. The English bulldog: a natural model of sleep-disordered breathing. J Appl Physiol 63: 1344-1350, 1987.
50. Hernandez AB, Kirkness JP, Smith PL, Schneider H, Polotsky M, Richardson RA, Hernandez WC, Schwartz AR. Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse. J Appl Physiol 112: 671-680, 2012.
51. Hoyos CM, Killick R, Yee BJ, Phillips CL, Grunstein RR, Liu PY. Cardiometabolic changes after continuous positive airway pressure for obstructive sleep apnoea: a randomised sham-controlled study. Thorax 67: 1081-1089, 2012.
52. Htoo AK, Greenberg H, Tongia S, Chen G, Henderson T, Wilson D, Liu. SF: Activation of nuclear factor kappaB in obstructive sleep apnea: a pathway leading to systemic inflammation. Sleep Breath 10: 43-50, 2006.
53. Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 165: 670-676, 2002.
54. Ip MS, Tse HF, Lam B, Tsang KW, Lam WK. Endothelial function in obstructive sleepapnea and response to treatment. Am J Respir Crit Care Med 169: 348-353, 2004.
55. Jelic S, Padeletti M, Kawut SM, Higgins C, Canfield SM, Onat D, Colombo PC, Basner RC, Factor P, LeJemtel TH. Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation 117: 2270-2278, 2008.
56. Joseph V, Pequignot JM, Van Reeth O. Neurochemical perspectives on the control of breathing during sleep. Respir Physiol Neurobiol 130: 253-263, 2002.
57. Jun J, Reinke C, Bedja D, Berkowitz D, Bevans-Fonti S, Li J, Barouch LA, Gabrielson K, Polotsky VY. Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 209: 381-386, 2010.
58. Jun J, Savransky V, Nanayakkara A, Bevans Li S, Smith PL, Polotsky VY. Intermittent hypoxia has organ-specific effects on oxidative stress. Am J Physiol Regul Integr Comp Physiol 295: R1274-R1281, 2008.
59. Jun JC, Drager LF, Najjar SS, Gottlieb SS, Brown CD, Smith PL, Schwartz AR, Polotsky VY. Effects of sleep apnea on nocturnal free fatty acids in subjects with heart failure. Sleep 34: 1207-1213, 2011.
60. Jun JC, Shin MK, Devera R, Yao Q, Mesarwi O, Bevans-Fonti S, Polotsky VY. Intermittent hypoxia-induced glucose intolerance is abolished by alpha-adrenergic blockade or adrenal medullectomy. Am J Physiol Endocrinol Metab 307: E1073-E1083, 2014.
61. Kallwitz ER, Herdegen J, Madura J, Jakate S, Cotler SJ. Liver enzymes and histology in obese patients with obstructive sleep apnea. J Clin Gastroenterol 41: 918-921, 2007.
62. Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, Somers VK. Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation 102: 2607-2610, 2000.
63. Kendzerska T, Gershon AS, Hawker G, Tomlinson G, Leung RS. Obstructive sleep apnea and incident diabetes. A historical cohort study. Am J Respir Crit Care Med 190: 218-225, 2014.
64. Kimoff RJ, Makino H, Horner RL, Kozar LF, Lue F, Slutsky AS, Phillipson EA. Canine model of obstructive sleep apnea: model description and preliminary application. J Appl Physiol 76: 1810-1817, 1994.
65. Kohler M, Pepperell JC, Davies RJ, Stradling JR. Continuous positive airway pressure and liver enzymes in obstructive sleep apnoea: data from a randomized controlled trial. Respiration 78: 141-146, 2009.
66. Krauss RM, Siri PW. Dyslipidemia in type 2 diabetes. Med Clin North Am 88: 897-909, 2004.
67. Kumar P, Prabhakar NR. Peripheral chemoreceptors: function and plasticity of the carotid body. In Comprehensive Physiology. Hoboken, NJ: Wiley, 2011, p. 141-219.
68. Kylintireas I, Craig S, Nethononda R, Kohler M, Francis J, Choudhury R, Stradling J, Neubauer S. Atherosclerosis and arterial stiffness in obstructive sleepapnea-a cardiovascular magnetic resonance study. Atherosclerosis 222: 483-489, 2012.
69. Lai CJ, Yang CC, Hsu YY, Lin YN, Kuo TB. Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats. J Appl Physiol 100: 1974-1982, 2006.
70. Lee EJ, Alonso LC, Stefanovski D, Strollo HC, Romano LC, Zou B, Singamsetty S, Yester KA, McGaffin KR, Garcia-Ocana A, O'Donnell CP. Time-dependent changes in glucose and insulin regulation during intermittent hypoxia and continuous hypoxia. Eur J Appl Physiol 113: 467-478, 2013.
71. Lesske J, Fletcher EC, Bao G, Unger T. Hypertension caused by chronic intermittent hypoxia-influence of chemoreceptors and sympathetic nervous system. J Hypertens 15: 1593-1603, 1997.
72. Li J, Grigoryev DN, Ye SQ, Thorne L, Schwartz AR, Smith PL, O'Donnell CP, Polotsky VY. Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol 99: 1643-1648, 2005.
73. Li J, Thorne N L, Punjabi NM, Sun CK, Schwartz AR, Smith PL, Marino RL, Rodriguez A, Hubbard WC, O'Donnell CP, Polotsky VY. Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 97: 698-706, 2005.
74. Li J, Bosch-Marce M, Nanayakkara A, Savransky V, Fried SK, Semenza GL, Polotsky VY. Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha. Physiol Genomics 25: 450-457, 2006.
75. Li RC, Haribabu B, Mathis SP, Kim J, Gozal D. Leukotriene B4 receptor-1 mediates intermittent hypoxia-induced atherogenesis. Am J Respir Crit Care Med 184: 124-131, 2011.
76. Liu A, Cardell J, Ariel D, Lamendola C, Abbasi F, Kim SH, Holmes TH, Tomasso V, Mojaddidi H, Grove K, Kushida CA, Reaven GM. Abnormalities of lipoprotein concentrations in obstructive sleep apnea are related to insulin resistance. Sleep 38: 793-799, 2015.
77. Lonergan RP 3rd, Ware JC, Atkinson RL, Winter WC, Suratt PM. Sleep apnea in obese miniature pigs. J Appl Physiol 84: 531-536, 1998.
78. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365: 1046-1053, 2005.
79. Marshall NS, Wong KK, Phillips CL, Liu PY, Knuiman MW, Grunstein RR. Is sleep apnea an independent risk factor for prevalent and incident diabetes in the Busselton Health Study? J Clin Sleep Med 5: 15-20, 2009.
80. Martínez-García MA, Soler-Cataluña JJ, Ejarque-Martínez L, Soriano Y, Román-Sánchez P, Illa FB, Canal JM, Durán-Cantolla J. Continuous positive airway pressure treatment reduces mortality in patients with ischemic stroke and obstructive sleep apnea: a 5-year follow-up study. Am J Respir Crit Care Med 180: 36-41, 2009.
81. Martínez-García MA, Campos-Rodríguez F, Catalán-Serra P, Soler-Cataluña JJ, Almeida-Gonzalez C, De la Cruz Morón I, Durán-Cantolla J, Montserrat JM. Cardiovascular mortality in obstructive sleep apnea in the elderly: role of long-term continuous positive airway pressure treatment: a prospective observational study. Am J Respir Crit Care Med 186: 909-916, 2012.
82. McEvoy RD, Anderson CS, Antic NA, Chen B, He Q, Heeley E, Huang S, Huang Y, Wang J, Zhong N. The sleep apnea cardiovascular endpoints (SAVE) trial: rationale and start-up phase. J Thorac Dis 2: 138-143, 2010.
83. Minoguchi K, Yokoe T, Tazaki T, Minoguchi H, Tanaka A, Oda N, Okada S, Ohta S, Naito H, Adachi M. Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am J Respir Crit Care Med 172: 625-630, 2005.
84. Mooe T, Franklin KA, Holmström K, Rabben T, Wiklund U. Sleepdisordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med 164: 1910-1913, 2001.
85. Moraes DJ, Da Silva MP, Bonagamba LG, Mecawi AS, Zoccal DB, Antunes-Rodrigues J, Varanda WA, Machado BH. Electrophysiological properties of rostral ventrolateral medulla presympathetic neurons modulated by the respiratory network in rats. J Neurosci 33: 19223-19237, 2013.
86. Moraes DJ, Zoccal DB, Machado BH. Medullary respiratory network drives sympathetic overactivity and hypertension in rats submitted to chronic intermittent hypoxia. Hypertension 60: 1374-1380, 2012.
87. Moraes DJ, Machado BH. Electrophysiological properties of laryngeal motoneurones in rats submitted to chronic intermittent hypoxia. J Physiol 593: 619-634, 2015.
88. Nakamura A, Zhang W, Yanagisawa M, Fukuda Y, Kuwaki T. Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice. J Appl Physiol 102: 241-248, 2007.
89. Newman AB, Nieto FJ, Guidry U, Lind BK, Redline S, Pickering TG, Quan SF. Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study. Am J Epidemiol 154: 50-59, 2001.
90. Nobili V, Cutrera R, Liccardo D, Pavone M, Devito R, Giorgio V, Verrillo E, Baviera G, Musso G. Obstructive sleep apnea syndrome affects liver histology and inflammatory cell activation in pediatric nonalcoholic fatty liver disease, regardless of obesity/insulin resistance. Am J Respir Crit Care Med 189: 66-76, 2014.
91. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 298: 299-308, 2007.
92. Norton CE, Jernigan NL, Kanagy NL, Walker BR, Resta TC. Intermittent hypoxia augments pulmonary vascular smooth muscle reactivity to NO: regulation by reactive oxygen species. J Appl Physiol 111: 980-988, 2011.
93. O'Donnell CP, King ED, Schwartz AR, Smith PL, Robotham JL. Effect of sleep deprivation on responses to airway obstruction in the sleeping dog. J Appl Physiol 77: 1811-1818, 1994.
94. Ohga E, Tomita T, Wada H, Yamamoto H, Nagase T, Ouchi Y. Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1. J Appl Physiol 94: 179-184, 2003.
95. Pamidi S, Tasali E. Obstructive sleep apnea and type 2 diabetes: is there a link? Front Neurol 3: 126, 2012.
96. Pamidi S, Wroblewski K, Stepien M, Sharif-Sidi K, Kilkus J, Whitmore H, Tasali E. Eight hours of nightly continuous positive airway pressure treatment of obstructive sleep apnea improves glucose metabolism in patients with prediabetes. A randomized controlled trial. Am J Respir Crit Care Med 192: 96-105, 2015.
97. Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC, Amodeo C, Bortolotto LA, Krieger EM, Bradley TD, Lorenzi-Filho G. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension 58: 811-817, 2011.
98. Pedrosa RP, Barros IM, Drager LF, Bittencourt MS, Medeiros AK, Carvalho LL, Lustosa TC, Carvalho MM, Ferreira MN, Lorenzi-Filho G, Costa LO. OSA is common and independently associated with hypertension and increased arterial stiffness in consecutive perimenopausal women. Chest 146: 66-72, 2014.
99. Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR. Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: implications for recurrent apneas. Proc Natl Acad Sci USA 100: 10073-10078, 2003.
100. Peng YJ, Prabhakar NR. Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity. J Appl Physiol 96: 1236-1242, 2004.
101. Peng YJ, Yuan G, Ramakrishnan D, Sharma SD, Bosch-Marce M, Kumar GK, Semenza GL, Prabhakar NR. Heterozygous HIF-1alpha deficiency impairs carotid body-mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxia. J Physiol 577: 705-716, 2006.
102. Peng YJ, Yuan G, Khan S, Nanduri J, Makarenko VV, Reddy VD, Vasavda C, Kumar GK, Semenza GL, Prabhakar NR. Regulation of hypoxia-inducible factor-α isoforms and redox state by carotid body neural activity in rats. J Physiol 592: 3841-3858, 2014.
103. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 342: 1378-1384, 2000.
104. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 177: 1006-1014, 2013.
105. Phillips CL, Yee BJ, Marshall NS, Liu PY, Sullivan DR, Grunstein RR. Continuous positive airway pressure reduces postprandial lipidemia in obstructive sleep apnea: a randomized, placebo-controlled crossover trial. Am J Respir Crit Care Med 184: 355-361, 2011.
106. Polotsky M, Elsayed-Ahmed AS, Pichard L, Harris CC, Smith PL, Schneider H, Kirkness JP, Polotsky V, Schwartz AR. Effects of leptin and obesity on the upper airway function. J Appl Physiol 112: 1637-1643, 2012.
107. Polotsky VY, Rubin AE, Balbir A, Dean T, Smith PL, Schwartz AR, O'Donnell CP. Intermittent hypoxia causes REM sleep deficits and decreases EEG delta power in NREM sleep in the C57BL/6J mouse. Sleep Med 7: 7-16, 2006.
108. Polotsky VY, Li J, Punjabi NM, Rubin AE, Smith PL, Schwartz AR, O'Donnell CP. Intermittent hypoxia increases insulin resistance in genetically obese mice. J Physiol 552: 253-264, 2003.
109. Polotsky VY, Patil SP, Savransky V, Lan A, Fonti S, Frame LA, Steele KE, Schweizter MA, Clark JM, Torbenson MS, Schwartz AR. Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity. Am J Respir Crit Care Med 179: 228-234, 2009.
110. Poulain L, Thomas A, Rieusset J, Casteilla L, Levy P, Arnaud C, Dematteis M. Visceral white fat remodelling contributes to intermittent hypoxia-induced atherogenesis. Eur Respir J 43: 513-522, 2014.
111. Punjabi NM, Beamer BA. Alterations in glucose disposal in sleepdisordered breathing. Am J Respir Crit Care Med 179: 235-240, 2009.
112. Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB, O'Connor GT, Rapoport DM, Redline S, Resnick HE, Robbins JA, Shahar E, Unruh ML, Samet JM. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med 6: e1000132, 2009.
113. Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL. Sleep-disordered breathing and insulin resistance in middleaged and overweight men. Am J Respir Crit Care Med 165: 677-682, 2002.
114. Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE. Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol 160: 521-530, 2004.
115. Radulovacki M, Trbovic S, Carley DW. Hypotension reduces sleep apneas in Zucker lean and Zucker obese rats. Sleep 19: 767-773, 1996.
116. Radulovacki M, Trbovic SM, Carley DW. Serotonin 5-HT3-receptor antagonist GR 38032F suppresses sleep apneas in rats. Sleep 21: 131-136, 1998.
117. Reichmuth KJ, Austin D, Skatrud JB, Young T. Association of sleep apnea and type II diabetes: a population-based study. Am J Respir Crit Care Med 172: 1590-1595, 2005.
118. Reinke C, Bevans-Fonti S, Drager LF, Shin MK, Polotsky VY. Effects of different acute hypoxic regimens on tissueoxygen profiles and metabolic outcomes. J Appl Physiol 111: 881-890, 2011.
119. Rey S, Del Rio R, Alcayaga J, Iturriaga R. Chronic intermittent hypoxia enhances cat chemosensory and ventilatory responses to hypoxia. J Physiol 560: 577-586, 2004.
120. Robinson GV, Pepperell JC, Segal HC, Davies RJ, Stradling JR. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 59: 777-782, 2004.
121. Rubin AE, Polotsky VY, Balbir A, Krishnan JA, Schwartz AR, Smith PL, Fitzgerald RS, Tankersley CG, Shirahata M, O'Donnell CP. Differences in sleep-induced hypoxia between A/J and DBA/2J mouse strains. Am J Respir Crit Care Med 168: 1520-1527, 2003.
122. Ryan S, Taylor CT, McNicholas WT. Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 112: 2660-2667, 2005.
123. Sato T, Saito H, Seto K, Takatsuji H. Sleep apneas and cardiac arrhythmias in freely moving rats. Am J Physiol Regul Integr Comp Physiol 259: R282-R287, 1990.
124. Savransky V, Nanayakkara A, Li J, Bevans S, Smith PL, Rodriguez A, Polotsky VY. Chronic intermittent hypoxia induces atherosclerosis. Am J Respir Crit Care Med 175: 1290-1297, 2007.
125. Savransky V, Nanayakkara A, Vivero A, Li J, Bevans S, Smith PL, Torbenson MS, Polotsky VY. Chronic intermittent hypoxia predisposes to liver injury. Hepatology 45: 1007-1013, 2007.
126. Savransky V, Bevans S, Nanayakkara A, Li J, Smith PL, Torbenson MS, Polotsky VY. Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. Am J Physiol Gastrointest Liver Physiol 293: G871-G877, 2007.
127. Savransky V, Jun J, Li J, Nanayakkara A, Fonti S, Moser AB, Steele KE, Schweitzer MA, Patil SP, Bhanot S, Schwartz AR, Polotsky VY. Dyslipidemia and atherosclerosis induced by chronic intermittent hypoxia are attenuated by deficiency of stearoyl coenzyme A desaturase. Circ Res 103: 1173-1180, 2008.
128. Schoorlemmer GH, Rossi MV, Tufik S, Cravo SL. A new method to produce obstructive sleep apnoea in conscious unrestrained rats. Exp Physiol 96: 1010-1018, 2011.
129. Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V, Somers VK. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 105: 2462-2464, 2002.
130. Shin MK, Han W, Bevans-Fonti S, Jun JC, Punjabi NM, Polotsky VY. The effect of adrenal medullectomy on metabolic responses to chronic intermittent hypoxia. Respir Physiol Neurobiol 203: 60-67, 2014.
131. Shin MK, Yao Q, Jun JC, Bevans-Fonti S, Yoo DY, Han W, Mesarwi O, Richardson R, Fu YY, Pasricha PJ, Schwartz AR, Shirahata M, Polotsky VY. Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia. J Appl Physiol 117: 765-776, 2014.
132. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 96: 1897-1904, 1995.
133. Song D, Fang G, Mao SZ, Ye X, Liu G, Gong Y, Liu SF. Chronic intermittenthypoxia induces atherosclerosis by NF-κB-dependent mechanisms. Biochim Biophys Acta 1822: 1650-1659, 2012.
134. Sood S, Liu X, Liu H, Horner RL. Genioglossus muscle activity and serotonergic modulation of hypoglossal motor output in obese Zucker rats. J Appl Physiol 102: 2240-2250, 2007.
135. Stanke-Labesque F, Pépin JL, de Jouvencel T, Arnaud C, Baguet JP, Petri MH, Tamisier R, Jourdil JF, Lévy P, Bäck M. Leukotriene B4 pathway activation and atherosclerosis in obstructive sleep apnea. J Lipid Res 53: 1944-1951, 2012.
136. Tagaito Y, Polotsky VY, Campen MJ, Wilson JA, Balbir A, Smith PL, Schwartz AR, O'Donnell CP. A model of sleep-disordered breathing in the C57BL/6J mouse. J Appl Physiol 91: 2758-2766, 2001.
137. Tahawi Z, Orolinova N, Joshua IG, Bader M, Fletcher EC. Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats. J Appl Physiol 90: 2007-2013, 2001.
138. Tanne F, Gagnadoux F, Chazouilleres O, Fleury B, Wendum D, Lasnier E, Lebeau B, Poupon R, Serfaty L. Chronic liver injury during obstructive sleep apnea. Hepatology 41: 1290-1296, 2005.
139. Trenell MI, Ward JA, Yee BJ, Phillips CL, Kemp GJ, Grunstein RR, Thompson CH. Influence of constant positive airway pressure therapy on lipid storage, muscle metabolism and insulin action in obese patients with severe obstructive sleep apnoea syndrome. Diabetes Obes Metab 9: 679-687, 2007.
140. Trzepizur W, Le Vaillant M, Meslier N, Pigeanne T, Masson P, Humeau MP, Bizieux-Thaminy A, Goupil F, Chollet S, Ducluzeau PH, Gagnadoux F; Institut de Recherche en Santé Respiratoire des Pays de la Loire (IRSR) Sleep Cohort Group. Independent association between nocturnal intermittent hypoxemia and metabolic dyslipidemia. Chest 143: 1584-1589, 2013.
141. Tuck SA, Dort JC, Olson ME, Remmers JE. Monitoring respiratory function and sleep in the obese Vietnamese pot-bellied pig. J Appl Physiol 87: 444-451, 1999.
142. Uchôa CH, Danzi-SoaresNde J, Nunes FS, de Souza AA, Nerbass FB, Pedrosa RP, César LA, Lorenzi-Filho G, Drager LF. Impact of OSA on cardiovascular events after coronary artery bypass sugery. Chest 147: 1352-1360, 2015.
143. Valham F, Mooe T, Rabben T, Stenlund H, Wiklund U, Franklin KA. Increased risk of stroke in patients with coronary artery disease and sleep apnea: a 10-year follow-up. Circulation 118: 955-960, 2008.
144. Veasey SC, Davis CW, Fenik P, Zhan G, Hsu YJ, Pratico D, Gow A. Long-term intermittent hypoxia in mice: protracted hypersomnolence with oxidative injury to sleep-wake brain regions. Sleep 27: 194-201, 2004.
145. Vgontzas AN, Papanicolaou DA, Bixler EO, Hopper K, Lotsikas A, Lin HM, Kales A, Chrousos GP. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 85: 1151-1158, 2000.
146. Wang N, Khan SA, Prabhakar NR, Nanduri J. Impairment of pancreatic β-cell function by chronicintermittent hypoxia. Exp Physiol 98: 1376-1385, 2013.
147. Yao Q, Shin MK, Jun JC, Hernandez KL, Aggarwal NR, Mock JR, Gay J, Drager LF, Polotsky VY. Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues. J Lipid Res 54: 1058-1065, 2013.
148. Zoccal DB, Bonagamba LG, Oliveira FR, Antunes-Rodrigues J, Machado BH. Increased sympathetic activity in rats submitted to chronic intermittent hypoxia. Exp Physiol 92: 79-85, 2007.
149. Zoccal DB, Machado BH. Sympathetic overactivity coupled with active expiration in rats submitted to chronic intermittent hypoxia. Respir Physiol Neurobiol 174: 98-101, 2010.
150. Zoccal DB, Machado BH. Coupling between respiratory and sympathetic activities as a novel mechanism underpinning neurogenic hypertension. Curr Hypertens Rep 13: 229-236, 2011.
151. Zoccal DB, Paton JF, Machado BH. Do changes in the coupling between respiratory and sympathetic activities contribute to neurogenic hypertension? Clin Exp Pharmacol Physiol 36: 1188-1196, 2009.
152. Zoccal DB, Simms AE, Bonagamba LG, Braga VA, Pickering AE, Paton JF, Machado BH. Increased sympathetic outflow in juvenile rats submitted to chronic intermittent hypoxia correlates with enhanced expiratory activity. J Physiol 586: 3253-3265, 2008.