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Published in:

01-04-2012

Cardiovascular Consequences of Sleep Apnea

Authors: Saeid Golbidi, Mohammad Badran, Najib Ayas, Ismail Laher

Published in: Lung | Issue 2/2012

Abstract

Sleep apnea is a common health concern that is characterized by repetitive episodes of asphyxia. This condition has been linked to serious long-term adverse effects such as hypertension, metabolic dysregulation, and cardiovascular disease. Although the mechanism for the initiation and aggravation of cardiovascular disease has not been fully elucidated, oxidative stress and subsequent endothelial dysfunction play major roles. Animal models, which have the advantage of being free of comorbidities and/or behavioral variables (that commonly occur in humans), allow invasive measurements under well-controlled experimental conditions, and as such are useful tools in the study of the pathophysiological mechanisms of sleep apnea. This review summarizes currently available information on the cardiovascular consequences of sleep apnea and briefly describes common experimental approaches useful to sleep apnea in different animal models.

Gupta RK, Chandra A, Verm AK, Kumar S (2010) Obstructive sleep apnoea: a clinical review. J Assoc Physicians India 58:438–441PubMed

Dempsey JA, Veasey SC, Morgan BJ, O’Donnell CP (2010) Pathophysiology of sleep apnea. Physiol Rev 90:47–112PubMedCrossRef

Partinen M (1995) Epidemiology of obstructive sleep apnea syndrome. Curr Opin Pulm Med 1:482–487PubMedCrossRef

Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328:1230–1235PubMedCrossRef

Lavie L, Lavie P (2009) Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link. Eur Respir J 33:1467–1484PubMedCrossRef

Peppard PE, Young T, Palta M, Skatrud J (2000) Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 342:1378–1384PubMedCrossRef

Kanagy NL (2009) Vascular effects of intermittent hypoxia. ILAR J 50:282–288PubMed

Drager LF, Bortolotto LA, Lorenzi MC, Figueiredo AC, Krieger EM, Lorenzi-Filho G (2005) Early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 172:613–618PubMedCrossRef

Itzhaki S, Lavie L, Pillar G, Tal G, Lavie P (2005) Endothelial dysfunction in obstructive sleep apnea measured by peripheral arterial tone response in the finger to reactive hyperemia. Sleep 28:594–600PubMed

10.

Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T (2008) Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. J Am Coll Cardiol 52:686–717PubMedCrossRef

11.

Golbidi S, Laher I (2010) Antioxidant therapy in human endocrine disorders. Med Sci Monit 16:RA9–RA24PubMed

12.

Schulz R, Mahmoudi S, Hattar K, Sibelius U, Olschewski H, Mayer K, Seeger W, Grimminger F (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea: impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162:566–570PubMed

13.

Dyugovskaya L, Lavie P, Lavie L (2002) Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Respir Crit Care Med 165:934–939PubMed

14.

Barceló A, Miralles C, Barbé F, Vila M, Pons S, Agustí AG (2000) Abnormal lipid peroxidation in patients with sleep apnoea. Eur Respir J 16:644–647PubMedCrossRef

15.

Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ (2003) 8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy. Chest 124:1386–1392PubMedCrossRef

16.

Christou K, Moulas AN, Pastaka C, Gourgoulianis KI (2003) Antioxidant capacity in obstructive sleep apnea patients. Sleep Med 4:225–228PubMedCrossRef

17.

Chen L, Einbinder E, Zhang Q, Hasday J, Balke CW, Scharf SM (2005) Oxidative stress and left ventricular function with chronic intermittent hypoxia in rats. Am J Respir Crit Care Med 172:915–920PubMedCrossRef

18.

Yamauchi M, Kimura H (2008) Oxidative stress in obstructive sleep apnea: putative pathways to the cardiovascular complications. Antioxid Redox Signal 10:755–768PubMedCrossRef

19.

Williams A, Scharf SM (2007) Obstructive sleep apnea, cardiovascular disease, and inflammation is NFkappaB the key? Sleep Breath 11:69–76PubMedCrossRef

20.

Minoguchi K, Yokoe T, Tazaki T, Minoguchi H, Tanaka A, Oda N, Okada S, Ohta S, Naito H, Adachi M (2005) Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am J Respir Crit Care Med 172:625–630PubMedCrossRef

21.

Ryan S, Taylor CT, McNicholas WT (2005) Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 112:2660–2667PubMedCrossRef

22.

Greenberg H, Ye X, Wilson D, Htoo AK, Hendersen T, Liu SF (2006) Chronic intermittent hypoxia activates nuclear factor-kappaB in cardiovascular tissues in vivo. Biochem Biophys Res Commun 343:591–596PubMedCrossRef

23.

Takahashi S, Nakamura Y, Nishijima T, Sakurai S, Inoue H (2005) Essential roles of angiotensin II in vascular endothelial growth factor expression in sleep apnea syndrome. Respir Med 99:1125–1131PubMedCrossRef

24.

Schulz R, Hummel C, Heinemann S, Seeger W, Grimminger F (2002) Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia. Am J Respir Crit Care Med 165:67–70PubMed

25.

Gjørup PH, Sadauskiene L, Wessels J, Nyvad O, Strunge B, Pedersen EB (2007) Abnormally increased endothelin-1 in plasma during the night in obstructive sleep apnea: relation to blood pressure and severity of disease. Am J Hypertens 20:44–52PubMedCrossRef

26.

Phillips SA, Olson EB, Morgan BJ, Lombard JH (2004) Chronic intermittent hypoxia impairs endothelium-dependent dilation in rat cerebral and skeletal muscle resistance arteries. Am J Physiol Heart Circ Physiol 286:H388–H393PubMedCrossRef

27.

Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, Somers VK (2000) Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation 102:2607–2610PubMed

28.

Ip MS, Lam B, Chan LY, Zheng L, Tsang KW, Fung PC, Lam WK (2000) Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure. Am J Respir Crit Care Med 162:2166–2171PubMed

29.

Chulz R, Schmidt D, Blum A, Lopes-Ribeiro X, Lucke C, Mayer K, Olschewski H, Seeger W, Grimminger F (2000) Decreased plasma levels of nitric oxide derivatives in obstructive sleep apnea: response to CPAP therapy. Thorax 55:1046–1051CrossRef

30.

Lavie L, Hefetz A, Luboshitzky R, Lavie P (2003) Plasma levels of nitric oxide and l-arginine in sleep apnea patients: effects of nCPAP treatment. J Mol Neurosci 21:57–63PubMedCrossRef

31.

Teramoto S, Kume H, Matsuse T, Ishii T, Miyashita A, Akishita M, Toba K, Ouchi Y (2003) Oxygen administration improves the serum level of nitric oxide metabolites in patients with obstructive sleep apnea syndrome. Sleep Med 4:403–407PubMedCrossRef

32.

Bayram NA, Ciftci B, Keles T, Durmaz T, Turhan S, Bozkurt E, Peker Y (2009) Endothelial function in normotensive men with obstructive sleep apnea before and 6 months after CPAP treatment. Sleep 32:1257–1263PubMed

33.

Schulz R, Seeger W, Grimminger F (2001) Serum nitrite/nitrate levels in obstructive sleep apnea. Am J Respir Crit Care Med 164:1997–1998PubMed

34.

Svatikova A, Wolk R, Wang HH, Otto ME, Bybee KA, Singh RJ, Somers VK (2004) Circulating free nitrotyrosine in obstructive sleep apnea. Am J Physiol 287:R284–R287

35.

Tabrizi-Fard MA, Maurer TS, Fung HL (1999) In vivo disposition of 3-nitro-l-tyrosine in rats: implications on tracking systemic peroxynitrite exposure. Drug Metab Dispos 27:429–431PubMed

36.

Jelic S, Padeletti M, Kawut SM, Higgins C, Canfield SM, Onat D, Colombo PC, Basner RC, Factor P, LeJemtel TH (2008) Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation 117:2270–2278PubMedCrossRef

37.

Tanaka T, Nakamura H, Yodoi J, Bloom ET (2005) Redox regulation of the signaling pathways leading to eNOS phosphorylation. Free Radic Biol Med 38:1231–1242PubMedCrossRef

38.

Yung LM, Leung FP, Yao X, Chen ZY, Huang Y (2006) Reactive oxygen species in vascular wall. Cardiovasc Hematol Disord Drug Targets 6:1–19PubMed

39.

Antoniades C, Shirodaria C, Warrick N, Cai S, de Bono J, Lee J, Leeson P, Neubauer S, Ratnatunga C, Pillai R, Refsum H, Channon KM (2006) 5-Methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation 114:1193–1201PubMedCrossRef

40.

Carlson J, Hedner J, Pettersson A (1997) Increased plasma concentration of ADMA, a naturally occurring nitric oxide synthesis inhibitor, in OSA patients. Am J Respir Crit Care Med 155:A869

41.

Ohike Y, Kozaki K, Iijima K, Eto M, Kojima T, Ohga E, Santa T, Imai K, Hashimoto M, Yoshizumi M, Ouchi Y (2005) Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure–possible involvement of nitric oxide and asymmetric NG, NG-dimethylarginine. Circ J 69:221–226PubMedCrossRef

42.

Bolli R, Shinmura K, Tang XL, Kodani E, Xuan YT, Guo Y, Dawn B (2002) Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning. Cardiovasc Res 55:506–519PubMedCrossRef

43.

Antman EM, DeMets D, Loscalzo J (2005) Cyclooxygenase inhibition and cardiovascular risk. Circulation 112:759–770PubMedCrossRef

44.

Lefebvre B, Godin-Ribuot D, Joyeux-Faure M, Caron F, Bessard G, Lévy P, Stanke-Labesque F (2006) Functional assessment of vascular reactivity after chronic intermittent hypoxia in the rat. Respir Physiol Neurobiol 150:278–286PubMedCrossRef

45.

Shamsuzzaman AS, Winnicki M, Lanfranchi P, Wolk R, Kara T, Accurso V, Somers VK (2002) Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation 105:2462–2464PubMedCrossRef

46.

Ohga E, Tomita T, Wada H, Yamamoto H, Nagase T, Ouchi Y (2003) Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1. J Appl Physiol 94:179–184PubMed

47.

Lavie L, Polotsky V (2009) Cardiovascular aspects in obstructive sleep apnea syndrome–molecular issues, hypoxia and cytokine profiles. Respiration 78:361–370PubMedCrossRef

48.

Zamarron C, García Paz V, Riveiro A (2008) Obstructive sleep apnea syndrome is a systemic disease. Current evidence. Eur J Intern Med 19:390–398PubMedCrossRef

49.

Hoffstein V, Herridge M, Mateika S, Redline S, Strohl KP (1994) Hematocrit levels in sleep apnea. Chest 106:787–791PubMedCrossRef

50.

Nobili L, Schiavi G, Bozano E, De Carli F, Ferrillo F, Nobili F (2000) Morning increase of whole blood viscosity in obstructive sleep apnea syndrome. Clin Hemorheol Microcirc 22:21–27PubMed

51.

Geiser T, Buck F, Meyer BJ, Bassetti C, Haeberli A, Gugger M (2002) In vivo platelet activation is increased during sleep in patients with obstructive sleep apnea syndrome. Respiration 69:229–234PubMedCrossRef

52.

Hui DS, Ko FW, Fok JP, Chan MC, Li TS, Tomlinson B, Cheng G (2004) The effects of nasal continuous positive airway pressure on platelet activation in obstructive sleep apnea syndrome. Chest 125:1768–1775PubMedCrossRef

53.

Wessendorf TE, Thilmann AF, Wang YM, Schreiber A, Konietzko N, Teschler H (2000) Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med 162:2039–2042PubMed

54.

Robinson GV, Pepperell JC, Segal HC, Davies RJ, Stradling JR (2004) Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 59:777–782PubMedCrossRef

55.

Zamarron C, Ricoy J, Riveiro A, Gude F (2008) Plasminogen activator inhibitor-1 in obstructive sleep apnea patients with and without hypertension. Lung 186:151–156PubMedCrossRef

56.

von Känel R, Loredo JS, Ancoli-Israel S, Mills PJ, Natarajan L, Dimsdale JE (2007) Association between polysomnographic measures of disrupted sleep and prothrombotic factors. Chest 131:733–739CrossRef

57.

Dimova EY, Samoylenko A, Kietzmann T (2004) Oxidative stress and hypoxia: implications for plasminogen activator inhibitor-1 expression. Antioxid Redox Signal 6:777–791PubMedCrossRef

58.

von Känel R, Dimsdale JE (2003) Hemostatic alterations in patients with obstructive sleep apnea and the implications for cardiovascular disease. Chest 124:1956–1967CrossRef

59.

Guyenet PG (2006) The sympathetic control of blood pressure. Nat Rev Neurosci 7:335–346PubMedCrossRef

60.

Leung RS, Bradley TD (2001) Sleep apnea and cardiovascular disease. Am J Respir Crit Care Med 164:2147–2165PubMed

61.

Brooks D, Horner RL, Floras JS, Kozar LF, Render-Teixeira CL, Phillipson EA (1999) Baroreflex control of heart rate in a canine model of obstructive sleep apnea. Am J Respir Crit Care Med 159:1293–1297PubMed

62.

Tkacova R, Dajani HR, Rankin F, Fitzgerald FS, Floras JS, Douglas Bradley T (2000) Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea. J Hypertens 18:1257–1262PubMedCrossRef

63.

Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR (2003) Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: implications for recurrent apneas. Proc Natl Acad Sci USA 100:10073–10078PubMedCrossRef

64.

Dematteis M, Godin-Ribuot D, Arnaud C, Ribuot C, Stanke-Labesque F, Pépin JL, Lévy P (2009) Cardiovascular consequences of sleep-disordered breathing: contribution of animal models to understanding the human disease. ILAR J 50:262–281PubMed

65.

Dematteis M, Julien C, Guillermet C, Sturm N, Lantuejoul S, Mallaret M, Lévy P, Gozal E (2008) Intermittent hypoxia induces early functional cardiovascular remodeling in mice. Am J Respir Crit Care Med 177:227–235PubMedCrossRef

66.

Kohler M, Stradling JR (2010) Mechanisms of vascular damage in obstructive sleep apnea. Nat Rev Cardiol 7:677–685PubMed

67.

Cutler MJ, Swift NM, Keller DM, Wasmund WL, Burk JR, Smith ML (2004) Periods of intermittent hypoxic apnea can alter chemoreflex control of sympathetic nerve activity in humans. Am J Physiol Heart Circ Physiol 287:H2054–H2060PubMedCrossRef

68.

Lai CJ, Yang CC, Hsu YY, Lin YN, Kuo TB (2006) Enhanced sympathetic outflow and decreased baroreflex sensitivity are associated with intermittent hypoxia-induced systemic hypertension in conscious rats. J Appl Physiol 100:1974–1982PubMedCrossRef

69.

Fletcher EC, Orolinova N, Bader M (2002) Blood pressure response to chronic episodic hypoxia: the renin-angiotensin system. J Appl Physiol 92:627–633PubMedCrossRef

70.

Somers VK, Dyken ME, Clary MP, Abboud FM (1995) Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 96:1897–1904PubMedCrossRef

71.

Fletcher EC, Miller J, Schaaf JW, Fletcher JG (1987) Urinary catecholamines before and after tracheostomy in patients with obstructive sleep apnea and hypertension. Sleep 10:35–44PubMed

72.

Kohler M, Pepperell JC, Casadei B, Craig S, Crosthwaite N, Stradling JR, Davies RJ (2008) CPAP and measures of cardiovascular risk in males with OSAS. Eur Respir J 32:1488–1496PubMedCrossRef

73.

Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF (2007) Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 176:706–712PubMedCrossRef

74.

Ziegler MG, Mills PJ, Loredo JS, Ancoli-Israel S, Dimsdale JE (2001) Effect of continuous positive airway pressure and placebo treatment on sympathetic nervous activity in patients with obstructive sleep apnea. Chest 120:887–893PubMedCrossRef

75.

Mills PJ, Kennedy BP, Loredo JS, Dimsdale JE, Ziegler MG (2006) Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea. J Appl Physiol 100:343–348PubMedCrossRef

76.

Norman D, Loredo JS, Nelesen RA, Ancoli-Israel S, Mills PJ, Ziegler MG, Dimsdale JE (2006) Effects of continuous positive airway pressure versus supplemental oxygen on 24-hour ambulatory blood pressure. Hypertension 47:840–845PubMedCrossRef

77.

Leiter JC, Knuth SL, Bartlett D Jr (1985) The effect of sleep deprivation on activity of the genioglossus muscle. Am Rev Respir Dis 132:1242–1245PubMed

78.

Cooper KR, Phillips BA (1982) Effect of short-term sleep loss on breathing. J Appl Physiol 53:855–858PubMed

79.

White DP, Douglas NJ, Pickett CK, Zwillich CW, Weil JV (1983) Sleep deprivation and the control of ventilation. Am Rev Respir Dis 128:984–986PubMed

80.

Tartar JL, Ward CP, Cordeira JW, Legare SL, Blanchette AJ, McCarley RW, Strecker RE (2008) Experimental sleep fragmentation and sleep deprivation in rats increases exploration in an open field test of anxiety while increasing plasma corticosterone levels. Behav Brain Res 197:450–453PubMedCrossRef

81.

Andersen ML, Martins PJF, D’Almeida V, Bignotto M, Tufik S (2005) Endocrinological and catecholaminergic alterations during sleep deprivation and recovery in male rats. J Sleep Res 14:83–90PubMedCrossRef

82.

Andersen ML, Martins PJF, D’Almeida V, Santos RF, Bignotto M, Tufik S (2004) Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in aged rats. Exp Gerontol 39:817–824PubMedCrossRef

83.

Everson CA, Crowley WR (2004) Reductions in circulating anabolic hormones induced by sustained sleep deprivation in rats. Am J Physiol Endocrinol Metab 286:E1060–E1070PubMedCrossRef

84.

Perry JC, D’Almeida V, Souza FG, Schoorlemmer GH, Colombari E, Tufik S (2007) Consequences of subchronic and chronic exposure to intermittent hypoxia and sleep deprivation on cardiovascular risk factors in rats. Respir Physiol Neurobiol 156:250–258PubMedCrossRef

85.

Yehuda S, Sredni B, Carrasso RL, Kenigsbuch-Sredni D (2009) REM sleep deprivation in rats results in inflammation and interleukin-17 elevation. J Interferon Cytokine Res 29:393–398PubMedCrossRef

86.

Irwin MR, Wang M, Ribeiro D, Cho HJ, Olmstead R, Breen EC, Martinez-Maza O, Cole S (2008) Sleep loss activates cellular inflammatory signaling. Biol Psychiatry 64:538–540PubMedCrossRef

87.

Van Dongen HP, Maislin G, Mullington JM, Dinges DF (2003) The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 26:117–126PubMed

88.

Haack M, Mullington JM (2005) Sustained sleep restriction reduces emotional and physical well-being. Pain 119:56–64PubMedCrossRef

89.

Nair D, Zhang SX, Ramesh V, Hakim F, Kaushal N, Wang Y, Gozal D (2011) Sleep fragmentation induces cognitive deficits via NADPH oxidase-dependent pathways in mouse. Am J Respir Crit Care Med. doi:10.1164/rccm.201107-1173OC

90.

Li J, Thorne LN, Punjabi NM, Sun CK, Schwartz AR, Smith PL, Marino RL, Rodriguez A, Hubbard WC, O’Donnell CP, Polotsky VY (2005) Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 97:698–706PubMedCrossRef

91.

Li J, Savransky V, Nanayakkara A, Smith PL, O’Donnell CP, Polotsky VY (2007) Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia. J Appl Physiol 102:557–563PubMedCrossRef

92.

Savransky V, Jun J, Li J, Nanayakkara A, Fonti S, Moser AB, Steele KE, Schweitzer MA, Patil SP, Bhanot S, Schwartz AR, Polotsky VY (2008) Dyslipidemia and atherosclerosis induced by chronic intermittent hypoxia are attenuated by deficiency of stearoyl coenzyme A desaturase. Circ Res 103:1173–1180PubMedCrossRef

93.

Drager LF, Jun JC, Polotsky VY (2010) Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea. Best Pract Res Clin Endocrinol Metab 24:843–851PubMedCrossRef

94.

Savransky V, Nanayakkara A, Vivero A, Li J, Bevans S, Smith PL, Torbenson MS, Polotsky VY (2007) Chronic intermittent hypoxia predisposes to liver injury. Hepatology 45:1007–1013PubMedCrossRef

95.

Pamidi S, Aronsohn RS, Tasali E (2010) Obstructive sleep apnea: role in the risk and severity of diabetes. Best Pract Res Clin Endocrinol Metab 24:703–715PubMedCrossRef

96.

Farré R, Montserrat JM, Navajas D (2008) Morbidity due to obstructive sleep apnea: insights from animal models. Curr Opin Pulm Med 14:530–536PubMedCrossRef

97.

Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL (2002) Sleep-disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med 165:677–682PubMed

98.

Punjabi NM, Beamer BA (2009) Alterations in glucose disposal in sleep-disordered breathing. Am J Respir Crit Care Med 179:235–240PubMedCrossRef

99.

Iiyori N, Alonso LC, Li J, Sanders MH, Garcia-Ocana A, O’Doherty RM, Polotsky VY, O’Donnell CP (2007) Intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity. Am J Respir Crit Care Med 175:851–857PubMedCrossRef

100.

Polotsky VY, Li J, Punjabi NM, Rubin AE, Smith PL, Schwartz AR, O’Donnell CP (2003) Intermittent hypoxia increases insulin resistance in genetically obese mice. J Physiol 552:253–264PubMedCrossRef

101.

Unger RH, Scherer PE (2010) Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends Endocrinol Metab 21:345–352PubMedCrossRef

102.

Magalang UJ, Cruff JP, Rajappan R, Hunter MG, Patel T, Marsh CB, Raman SV, Parinandi NL (2009) Intermittent hypoxia suppresses adiponectin secretion by adipocytes. Exp Clin Endocrinol Diabetes 117:129–134PubMedCrossRef

103.

Jun J, Polotsky VY (2007) Sleep disordered breathing and metabolic effects: evidence from animal models. Sleep Med Clin 2:263–277PubMedCrossRef

104.

Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 11:183–190PubMedCrossRef

105.

Parlapiano C, Borgia MC, Minni A, Alessandri N, Basal I, Saponara M (2005) Cortisol circadian rhythm and 24-hour Holter arterial pressure in OSAS patients. Endocr Res 31:371–374PubMedCrossRef

106.

Wang TY, Chen XQ, Du JZ, Xu NY, Wei CB, Vale WW (2004) Corticotropin-releasing factor receptor type 1 and 2 mRNA expression in the rat anterior pituitary is modulated by intermittent hypoxia, cold and restraint. Neuroscience 128:111–119PubMedCrossRef

107.

Neuzeret PC, Gormand F, Reix P, Parrot S, Sastre JP, Buda C, Guidon G, Sakai K, Lin JS (2011) A new animal model of obstructive sleep apnea responding to continuous positive airway pressure. Sleep 34:541–548PubMed

108.

Hendricks JC, Kline LR, Kovalski RJ, O’Brien JA, Morrison AR, Pack AI (1987) The English bulldog: a natural model of sleep-disordered breathing. J Appl Physiol 63:1344–1350PubMed

109.

Veasey SC, Fenik P, Panckeri K, Pack AI, Hendricks JC (1999) The effects of trazodone with l-tryptophan on sleep-disordered breathing in the English bulldog. Am J Respir Crit Care Med 160:1659–1667PubMed

110.

Veasey SC, Chachkes J, Fenik P, Hendricks JC (2001) The effects of ondansetron on sleep-disordered breathing in the English bulldog. Sleep 24:155–160PubMed

111.

Carley DW, Radulovacki M (2003) Sleep-related breathing disorders, experimental models and therapeutic potential. Marcel Dekker, New York

112.

Lonergan RP 3rd, Ware JC, Atkinson RL, Winter WC, Suratt PM (1998) Sleep apnea in obese miniature pigs. J Appl Physiol 84:531–536PubMed

113.

Tuck SA, Dort JC, Olson ME, Remmers JE (1999) Monitoring respiratory function and sleep in the obese Vietnamese pot-bellied pig. J Appl Physiol 87:444–451PubMed

114.

Philip P, Gross CE, Taillard J, Bioulac B, Guilleminault C (2005) An animal model of a spontaneously reversible obstructive sleep apnea syndrome in the monkey. Neurobiol Dis 20:428–431PubMedCrossRef

115.

Van Lunteren E (1996) Effects of genetic obesity on rat upper airway muscle and diaphragm contractile properties. Eur Respir J 9:2139–2144PubMed

116.

Alonso-Galicia M, Brands MW, Zappe DH, Hall JE (1996) Hypertension in obese Zucker rats. Role of angiotensin II and adrenergic activity. Hypertension 28:1047–1054PubMed

117.

Fredersdorf S, Thumann C, Ulucan C, Griese DP, Luchner A, Riegger GA, Kromer EP, Weil J (2004) Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats. Cardiovasc Pathol 13:11–19PubMedCrossRef

118.

Lee SD, Nakano H, Farkas GA (2005) Adenosinergic modulation of ventilation in obese Zucker rats. Obes Res 13:545–555PubMedCrossRef

119.

Radulovacki M, Trbovic S, Carley DW (1996) Hypotension reduces sleep apneas in Zucker lean and Zucker obese rats. Sleep 19:767–773PubMed

120.

Nakano H, Magalang UJ, Lee SD, Krasney JA, Farkas GA (2001) Serotonergic modulation of ventilation and upper airway stability in obese Zucker rats. Am J Respir Crit Care Med 163:1191–1197PubMed

121.

Brennick MJ, Pickup S, Cater JR, Kuna ST (2006) Phasic respiratory pharyngeal mechanics by magnetic resonance imaging in lean and obese Zucker rats. Am J Respir Crit Care Med 173:1031–1037PubMedCrossRef

122.

Lee SD, Kuo WW, Bau DT, Ko FY, Wu FL, Kuo CH, Tsai FJ, Wang PS, Lu MC, Huang CY (2008) The coexistence of nocturnal sustained hypoxia and obesity additively increases cardiac apoptosis. J Appl Physiol 104:1144–1153PubMedCrossRef

123.

Wajant H (2002) The Fas signaling pathway: more than a paradigm. Science 296:1635–1636PubMedCrossRef

124.

Schneider P, Bodmer JL, Holler N, Mattmann C, Scuderi P, Terskikh A, Peitsch MC, Tschopp J (1997) Characterization of Fas (Apo-1, CD95)-Fas ligand interaction. J Biol Chem 272:18827–18833PubMedCrossRef

125.

Sato T, Saito H, Seto K, Takatsuji H (1990) Sleep apneas and cardiac arrhythmias in freely moving rats. Am J Physiol 259:R282–R287PubMed

126.

Mendelson WB, Martin JV, Perlis M, Giesen H, Wagner R, Rapoport SI (1988) Periodic cessation of respiratory effort during sleep in adult rats. Physiol Behav 43:229–234PubMedCrossRef

127.

Thomas AJ, Austin W, Friedman L, Strohl KP (1992) A model of ventilatory instability induced in the unrestrained rat. J Appl Physiol 73:1530–1536PubMed

128.

Carley DW, Trbovic S, Radulovacki M (1996) Sleep apnea in normal and REM sleep-deprived normotensive Wistar-Kyoto and spontaneously hypertensive (SHR) rats. Physiol Behav 59:827–831PubMedCrossRef

129.

Kuo TB, Lai CJ, Shaw FZ, Lai CW, Yang CC (2004) Sleep-related sympathovagal imbalance in SHR. Am J Physiol 286:H1170–H1176

130.

Plante GE (2006) Sleep and vascular disorders. Metabolism 55:s45–s49PubMedCrossRef

131.

Carley DW, Berecek K, Videnovic A, Radulovacki M (2000) Sleep-disordered respiration in phenotypically normotensive, genetically hypertensive rats. Am J Respir Crit Care Med 162:1474–1479PubMed

132.

Carley DW, Trbovic SM, Bozanich A, Radulovacki M (1997) Cardiopulmonary control in sleeping Sprague-Dawley rats treated with hydralazine. J Appl Physiol 83:1954–1961PubMed

133.

Trbovic SM, Radulovacki M, Carley DW (1997) Protoveratrines A and B increase sleep apnea index in Sprague-Dawley rats. J Appl Physiol 83:1602–1606PubMed

134.

Carley DW, Radulovacki M (1999) Mirtazapine, a mixed-profile serotonin agonist/antagonist, suppresses sleep apnea in the rat. Am J Respir Crit Care Med 160:1824–1829PubMed

135.

Carley DW, Olopade C, Ruigt GS, Radulovacki M (2007) Efficacy of mirtazapine in obstructive sleep apnea syndrome. Sleep 30:35–41PubMed

136.

Peters LL, Robledo RF, Bult CJ, Churchill GA, Paigen BJ, Svenson KL (2007) The mouse as a model for human biology: a resource guide for complex trait analysis. Nat Rev Genet 8:58–69PubMedCrossRef

137.

Nakamura A, Kuwaki T (2003) Sleep apnea in mice: a useful animal model for study of SIDS? Early Hum Dev 75:S167–S174PubMedCrossRef

138.

Yamauchi M, Kimura H, Strohl KP (2010) Mouse models of apnea: strain differences in apnea expression and its pharmacologic and genetic modification. Adv Exp Med Biol 669:303–307PubMedCrossRef

139.

Berry-Kravis EM, Zhou L, Rand CM, Weese-Mayer DE (2006) Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype. Am J Respir Crit Care Med 174:1139–1144PubMedCrossRef

140.

Burton MD, Kawashima A, Brayer JA, Kazemi H, Shannon DC, Schuchardt A, Costantini F, Pachnis V, Kinane TB (1997) RET proto-oncogene is important for the development of respiratory CO₂ sensitivity. J Auton Nerv Syst 63:137–143PubMedCrossRef

141.

Tsujino N, Sakurai T (2009) Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol Rev 61:162–176PubMedCrossRef

142.

Nakamura A, Zhang W, Yanagisawa M, Fukuda Y, Kuwaki T (2007) Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice. J Appl Physiol 102:241–248PubMedCrossRef

143.

Baekey DM, Feng P, Decker MJ, Strohl KP (2009) Breathing and sleep: measurement methods, genetic influences, and developmental impacts. ILAR J 50:248–261PubMed

144.

Brennick MJ, Pack AI, Ko K, Kim E, Pickup S, Maislin G, Schwab RJ (2009) Altered upper airway and soft tissue structures in the New Zealand Obese mouse. Am J Respir Crit Care Med 179:158–169PubMedCrossRef

145.

Brennick MJ, Kuna ST, Pickup S, Cater J, Schwab RJ (2011) Respiratory modulation of the pharyngeal airway in lean and obese mice. Respir Physiol Neurobiol 175:296–302PubMedCrossRef

146.

Katayama K, Smith CA, Henderson KS, Dempsey JA (2007) Chronic intermittent hypoxia increases the CO₂ reserve in sleeping dogs. J Appl Physiol 103:1942–1949PubMedCrossRef

147.

Kimoff RJ, Brooks D, Horner RL, Kozar LF, Render-Teixeira CL, Champagne V, Mayer P, Phillipson EA (1997) Ventilatory and arousal responses to hypoxia and hypercapnia in a canine model of obstructive sleep apnea. Am J Respir Crit Care Med 156:886–894PubMed

148.

Launois SH, Averill N, Abraham JH, Kirby DA, Weiss JW (2001) Cardiovascular responses to nonrespiratory and respiratory arousals in a porcine model. J Appl Physiol 90:114–120PubMed

149.

White SG, Fletcher EC, Miller CC 3rd (1995) Acute systemic blood pressure elevation in obstructive and nonobstructive breath hold in primates. J Appl Physiol 79:324–330PubMed

150.

Farré R, Rotger M, Montserrat JM, Calero G, Navajas D (2003) Collapsible upper airway segment to study the obstructive sleep apnea/hypopnea syndrome in rats. Respir Physiol Neurobiol 136:199–209PubMedCrossRef

151.

Nácher M, Serrano-Mollar A, Farré R, Panés J, Seguí J, Montserrat JM (2007) Recurrent obstructive apneas trigger early systemic inflammation in a rat model of sleep apnea. Respir Physiol Neurobiol 155:93–96PubMedCrossRef

152.

Schneider H, Schaub CD, Chen CA, Andreoni KA, Schwartz AR, Smith PL, Robotham JL, O’Donnell CP (2000) Effects of arousal and sleep state on systemic and pulmonary hemodynamics in obstructive apnea. J Appl Physiol 88:1084–1092PubMed

153.

Schoorlemmer GH, Rossi MV, Tufik S, Cravo SL (2011) A new method to produce obstructive sleep apnoea in conscious unrestrained rats. Exp Physiol 96:1010–1018PubMed

154.

Farré R, Nácher M, Serrano-Mollar A, Gáldiz JB, Alvarez FJ, Navajas D, Montserrat JM (2007) Rat model of chronic recurrent airway obstructions to study the sleep apnea syndrome. Sleep 30:930–933PubMed

155.

Hamrahi H, Stephenson R, Mahamed S, Liao KS, Horner RL (2001) Selected Contribution: Regulation of sleep-wake states in response to intermittent hypoxic stimuli applied only in sleep. J Appl Physiol 90:2490–2501PubMed

156.

Bonsignore MR, Marrone O, Insalaco G, Bonsignore G (1994) The cardiovascular effects of obstructive sleep apnoeas: analysis of pathogenic mechanisms. Eur Respir J 7:786–805PubMedCrossRef

157.

McGuire M, Bradford A (2001) Chronic intermittent hypercapnic hypoxia increases pulmonary arterial pressure and haematocrit in rats. Eur Respir J 18:279–285PubMedCrossRef

158.

de Frutos S, Duling L, Alò D, Berry T, Jackson-Weaver O, Walker M, Kanagy N, González Bosc L (2008) NFATc3 is required for intermittent hypoxia-induced hypertension. Am J Physiol Heart Circ Physiol 294:H2382–H2390PubMedCrossRef

159.

Dunleavy M, Dooley M, Cox D, Bradford A (2005) Chronic intermittent asphyxia increases platelet reactivity in rats. Exp Physiol 90:411–416PubMedCrossRef

160.

Carreras A, Wang Y, Gozal D, Montserrat JM, Navajas D, Farré R (2011) Non-invasive system for applying airway obstructions to model obstructive sleep apnea in mice. Respir Physiol Neurobiol 175:164–168PubMedCrossRef

161.

Lesske J, Fletcher EC, Bao G, Unger T (1997) Hypertension caused by chronic intermittent hypoxia–influence of chemoreceptors and sympathetic nervous system. J Hypertens 15:1593–1603PubMedCrossRef

162.

Bradford A (2004) Effects of chronic intermittent asphyxia on haematocrit, pulmonary arterial pressure and skeletal muscle structure in rats. Exp Physiol 89:44–52PubMedCrossRef

163.

Allahdadi KJ, Walker BR, Kanagy NL (2005) Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension. Hypertension 45:705–709PubMedCrossRef

164.

Fletcher EC (2001) Invited review: Physiological consequences of intermittent hypoxia: systemic blood pressure. J Appl Physiol 90:1600–1605PubMedCrossRef

165.

Kanagy NL, Walker BR, Nelin LD (2001) Role of endothelin in intermittent hypoxia-induced hypertension. Hypertension 37:511–515PubMed

166.

Julien C, Bayat S, Lévy P (2003) Vascular reactivity to norepinephrine and acetylcholine after chronic intermittent hypoxia in mice. Respir Physiol Neurobiol 139:21–32PubMedCrossRef

167.

Tahawi Z, Orolinova N, Joshua IG, Bader M, Fletcher EC (2001) Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats. J Appl Physiol 90:2007–2013PubMed

168.

McNulty PH, Ng C, Liu WX, Jagasia D, Letsou GV, Baldwin JC, Soufer R (1996) Autoregulation of myocardial glycogen concentration during intermittent hypoxia. Am J Physiol 271:R311–R319PubMed

169.

Li J, Grigoryev DN, Ye SQ, Thorne L, Schwartz AR, Smith PL, O’Donnell CP, Polotsky VY (2005) Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol 99:1643–1648PubMedCrossRef

170.

Li J, Bosch-Marce M, Nanayakkara A, Savransky V, Fried SK, Semenza GL, Polotsky VY (2006) Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha. Physiol Genomics 25:450–457PubMedCrossRef

171.

Li J, Nanayakkara A, Jun J, Savransky V, Polotsky VY (2007) Effect of deficiency in SREBP cleavage-activating protein on lipid metabolism during intermittent hypoxia. Physiol Genomics 31:237–280

172.

Feng SZ, Tian JL, Zhang Q, Wang H, Sun N, Zhang Y, Chen BY (2011) An experimental research on chronic intermittent hypoxia leading to liver injury. Sleep Breath 15:493–502PubMedCrossRef

173.

Liu JN, Zhang JX, Lu G, Qiu Y, Yang D, Yin GY, Zhang XL (2010) The effect of oxidative stress in myocardial cell injury in mice exposed to chronic intermittent hypoxia. Chin Med J (Engl) 123:74–78

174.

Matsumoto C, Hayashi T, Kitada K, Yamashita C, Miyamura M, Mori T, Ukimura A, Ohkita M, Jin D, Takai S, Miyazaki M, Okada Y, Kitaura Y, Matsumura Y (2009) Chymase plays an important role in left ventricular remodeling induced by intermittent hypoxia in mice. Hypertension 54:164–171PubMedCrossRef

175.

Nácher M, Farré R, Montserrat JM, Torres M, Navajas D, Bulbena O, Serrano-Mollar A (2009) Biological consequences of oxygen desaturation and respiratory effort in an acute animal model of obstructive sleep apnea (OSA). Sleep Med 10:892–897PubMedCrossRef

176.

Savransky V, Bevans S, Nanayakkara A, Li J, Smith PL, Torbenson MS, Polotsky VY (2007) Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. Am J Physiol Gastrointest Liver Physiol 293:G871–G877PubMedCrossRef

177.

Troncoso Brindeiro CM, da Silva AQ, Allahdadi KJ, Youngblood V, Kanagy NL (2007) Reactive oxygen species contribute to sleep apnea-induced hypertension in rats. Am J Physiol Heart Circ Physiol 293:H2971–H2976PubMedCrossRef

178.

Park AM, Suzuki YJ (2007) Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice. J Appl Physiol 102:1806–1814PubMedCrossRef

179.

Rosa DP, Martinez D, Picada JN, Semedo JG, Marroni NP (2011) Hepatic oxidative stress in an animal model of sleep apnoea: effects of different duration of exposure. Comp Hepatol 10:1PubMedCrossRef

180.

Xu W, Chi L, Row BW, Xu R, Ke Y, Xu B, Luo C, Kheirandish L, Gozal D, Liu R (2004) Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea. Neuroscience 126:313–323PubMedCrossRef

181.

Allahdadi KJ, Cherng TW, Pai H, Silva AQ, Walker BR, Nelin LD, Kanagy NL (2008) Endothelin type A receptor antagonist normalizes blood pressure in rats exposed to eucapnic intermittent hypoxia. Am J Physiol Heart Circ Physiol 295:H434–H440PubMedCrossRef

182.

Knight WD, Little JT, Carreno FR, Toney GM, Mifflin SW, Cunningham JT (2011) Chronic intermittent hypoxia increases blood pressure and expression of FosB/DeltaFosB in central autonomic regions. Am J Physiol Regul Integr Comp Physiol 301:R131–R139PubMedCrossRef

183.

Kalaria RN, Spoors L, Laude EA, Emery CJ, Thwaites-Bee D, Fairlie J, Oakley AE, Barer DH, Barer GR (2004) Hypoxia of sleep apnoea: cardiopulmonary and cerebral changes after intermittent hypoxia in rats. Respir Physiol Neurobiol 140:53–62PubMedCrossRef

184.

Iturriaga R, Moya EA, Del Rio R (2010) Cardiorespiratory alterations induced by intermittent hypoxia in a rat model of sleep apnea. Adv Exp Med Biol 669:271–274PubMedCrossRef

185.

Othman M, Gordon SP, Iscoe S (2010) Repeated inspiratory occlusions in anesthetized rats acutely increases blood coagulability as assessed by thromboelastography. Respir Physiol Neurobiol 171:61–66PubMedCrossRef

Title: Cardiovascular Consequences of Sleep Apnea
Authors: Saeid Golbidi
Mohammad Badran
Najib Ayas
Ismail Laher
Publication date: 01-04-2012
Publisher: Springer-Verlag
Published in: Lung / Issue 2/2012
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-011-9340-1

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