Abstract
Individuals with obstructive sleep apnea syndrome (OSAS) are at high risk for cardiovascular morbidity and mortality. The effects of OSAS severity and nocturnal continuous positive airway pressure (CPAP) on daytime baroreflex sensitivity (BRS) and nitric oxide (NO) production were investigated in OSAS patients. Fifty-one consecutive males with OSAS and 29 age-matched healthy men underwent the Valsalva test and standard polysomnography. Patients with an apnea-hypopnea index (AHI) of ≥20 episodes per hour were randomized to receive CPAP treatment for 3 months (n=14) or no such treatment (n=19). The BRS index measured from the overshoot phase (phase IV) of the Valsalva maneuver and plasma NO concentration were significantly lower, whereas the AHI, oxygen desaturation time, arousal index, percentage of sleep stage 1, and systolic blood pressure were significantly greater, in patients with an AHI of ≥20/h than in those with an AHI of <20/h or in controls. The 24-h urinary excretion of norepinephrine was significantly reduced and the plasma NO concentration was significantly increased after one night of CPAP. The BRS index for phase IV and the Valsalva ratio were significantly increased in the CPAP group after the 3-month treatment period but remained unchanged in the non-CPAP group of OSAS patients. The daytime BRS index and NO production were thus inversely related to the severity of OSAS, and successful CPAP treatment improved these parameters in patients with moderate to severe OSAS. CPAP may therefore reduce the risk of cardiovascular complications due to endothelial dysfunction or increased sympathetic activity.
Similar content being viewed by others
Article PDF
References
Nieto FJ, Young TB, Lind BK, et al: Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. The Sleep Health Study. JAMA 2000; 283: 1829–1836.
Shahar E, Whitney CW, Redline S, et al: Sleep-disordered breathing and cardiovascular disease. Cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 2001; 163: 19–25.
Lavie P, Herer P, Peled R, et al: Mortality in sleep apnea patients: a multivariate analysis of risk factors. Sleep 1995; 18: 149–157.
Martine 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 2005; 365: 1046–1053.
Tanigawa T, Tachibana N, Yamagishi K, et al: Relationship between sleep-disordered breathing and blood pressure levels in community-based samples of Japanese men. Hypertens Res 2004; 27: 479–484.
Bradley TD, Floras JS : Sleep apnea and heart failure. Part I: Obstructive sleep apnea. Circulation 2003; 107: 1671–1678.
Usui K, Bradley D, Spaak J, et al: Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure. J Am Coll Cardiol 2005; 45: 2008–2011.
Spaak J, Egri ZJ, Kubo T, et al: Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea. Hypertension 2005; 46: 1327–1332.
Noda A, Okada T, Hayashi H, et al: 24-hour ambulatory blood pressure variability in obstructive sleep apnea syndrome. Chest 1993; 103: 1343–1347.
Noda A, Okada T, Yasuma F, et al: Cardiac hypertrophy in obstructive sleep apnea syndrome. Chest 1995; 107: 1538–1544.
Noda A, Yasuma F, Okada T, et al: Influence of movement arousal on circadian rhythm of blood pressure in obstructive sleep apnea syndrome. J Hypertens 2000; 18: 539–544.
Levy D, Garrison RJ, Savage DD, et al: Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561–1566.
Noda A, Okada T, Yasuma F, et al: Prognosis of the middle-aged and aged patients with obstructive sleep apnea syndrome. Psychiatr Clin Neurosci 1998; 52: 79–85.
Mortara A, Rovere MTL, Pinna GD, et al: Arterial baroreflex modulation of heart rate in chronic heart failure. Clinical and hemodynamic correlates and prognostic implications. Circulation 1997; 96: 3450–3458.
La Rovere MT, Bigger JT, Marcus FI, et al: Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet 1998; 351: 478–484.
Chowdhary S, Townend JN : Role of nitric oxide in the regulation of cardiovascular autonomic control. Clin Sci 1999; 97: 5–17.
Liu J, Murakami H, Zucker IH : Effects of NO on baroreflex control of heart rate and renal nerve activity in conscious rabbits. Am J Physiol 1996; 270: 1361–1370.
Kato M, Roberts-Thomson P, Phillips BG, et al: Impairment of endothelium-dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation 2000; 102: 2607–2610.
Ip MS, Lam B, Chan LY, et al: Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure. Am J Respir Crit Care Med 2000; 162: 2166–2171.
The Report of an American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults : recommendation for syndrome definition and measurement techniques in clinical research. Sleep 1999; 22: 667–689.
Rechtschaffen A, Kales A : A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stage of Human Subjects. Washington, DC, US Government Printing Office, 1968.
Sleep Disorders Atlas Task Force of the American Sleep Disorders Association : EEG arousals: scoring rules and examples. Sleep 1992; 15: 173–184.
He J, Kryger MH, Zorick FJ : Mortality and apnea index in obstructive sleep apnea: experience in 385 male patients. Chest 1988; 94: 9–14.
Kitaichi K, Wang L, Takagi K, et al: Decreased antipyrine clearance following endotoxin administration: in vivo evidence of the role of nitric oxide. Antimicrob Agents Chemother 1999; 43: 2697–2701.
Benarroch EE, Sandoni P, Low PA : The Valsalva maneuver, in Low PA ( ed): Clinical Autonomic Disorders. Boston, Toronto, and London, Little, Brown Co, 1993, pp 209–215.
Huikuri H, Pikkujamsa SM, Airaksinen J, et al: Sex-related differences in autonomic modulation of heart rate in middle-aged subjects. Circulation 1996; 94: 122–125.
Somers VK, Dyken ME, Mark AL, Abboud FM : Sympathetic-nerve activity during sleep in normal subjects. N Engl J Med 1993; 328: 303–307.
Somers VK, Dyken ME, Clary MP, et al: Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995; 96: 1897–1904.
Young T, Peppard P, Palta M : Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997; 157: 1746–1752.
Cortelli P, Parchi P, Sforza E, et al: Cardiovascular autonomic dysfunction in normotensive awake subjects with obstructive sleep apnea syndrome. Clin Autonom Res 1994; 4: 57–62.
Sforza E, Parchi P, Contin M, et al: Do autonomic cardiovascular reflexes predict the nocturnal rise in blood pressure in obstructive sleep apnea syndrome? Blood Pressure 1994; 3: 295–302.
Eckberg DL : Parasympathetic cardiovascular control in human disease: a critical review of methods and results. Am J Physiol 1980; 239: H581–H593.
Palmero HA, Caeiro TF, Iosa DJ, Bas J : Baroreceptor reflex sensitivity index derived from phase 4 of the Valsalva maneuver. Hypertension 1981; 3 ( Suppl II): II-134–II-137.
Wang W, Ma R : Cardiac sympathetic afferent reflexes in heart failure. Heart Fail 2000; 5: 57–71.
Noda A, Yasuma F, Okada T, et al: Circadian rhythm of autonomic activity in patients with obstructive sleep apnea syndrome. Clin Cardiol 1998; 21: 271–276.
Singh JP, Larson MG, Tsuji H, et al: Reduced heart rate variability and new-onset hypertension: insights into pathogenesis of hypertension: the Framingham Heart Study. Hypertension 1998; 32: 293–297.
Eckberg D : Parasympathetic cardiovascular control in human disease: a critical review of methods and results. Am J Physiol 1980; 239: H581–H593.
Nelson RA, Yu H, Ziegler MG, et al: Continuous positive airway pressure normalizes cardiac autonomic and hemodynamic responses to a laboratory stressor in apneic patients. Chest 2001; 119: 1092–1101.
Khoo MC, Belozeroff V, Berry RB, et al: Cardiac autonomic control in obstructive sleep apnea. Long-term CPAP therapy. Am J Respir Crit Care Med 2001; 164: 807–812.
Narkiewicz K, Pesek CA, Kato M, Phillips BG, Davison DE, Somers VK : Baroreflex control of sympathetic nerve activity and heart rate in obstructive sleep apnea. Hypertension 1998; 32: 1039–1043.
Tkacova R, Dajani HR, Rankin F, et al: Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea. J Hypertens 2000; 18: 1257–1262.
Bonsignore MR, Prati G, Insalaco G, et al: Continuous positive airway pressure treatment improves baroreflex control of heart rate during sleep in severe obstructive sleep apnea syndrome. Am J Respir Crit Care Med 2002; 166: 279–286.
Waravdekar NV, Sinoway LI, Zwillich CW, et al: Influence of treatment on muscle sympathetic nerve activity in sleep apnea. Am J Respir Crit Care Med 1996; 153: 1333–1338.
Narkiewicz K, Borne PJH, Pesek CA, et al: Selective potentiation of peripheral chemoreflex sensitivity in obstructive sleep apnea. Circulation 1999; 99: 1183–1189.
Narkiewicz K, Kato M, Phillips BG, et al: Nocturnal continuous positive airway pressure decreases daytime sympathetic traffic in obstructive sleep apnea. Circulation 1999; 100: 2332–2335.
Ogawa Y, Kanbayashi T, Saito Y, et al: Total sleep deprivation elevates blood pressure through arterial baroreflex resetting: a study with microneurographic technique. Sleep 2003; 26: 986–989.
Bristow JR, Honour AJ, Pickring TG, et al: Cardiovascular and respiratory change during sleep in normal and hypertensive subjects. Cardiovasc Res 1969; 3: 476–485.
Panza J, Quyyumi AA, Brush JE, Epstein SE : Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Eng J Med 1990; 323: 22–27.
Lin KY, Asagami T, Tsao PS, et al: Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 2002; 106: 987–992.
Hatta T, Nakata T, Harada S, et al: Lowering of blood pressure improves endothelial dysfunction by increase of nitric oxide production in hypertensive rats. Hypertens Res 2002; 25: 455–460.
Furumoto T, Saito N, Dong J, et al: Association of cardiovascular risk factors and endothelial dysfunction in Japanese hypertensive patients: implications for early atherosclerosis. Hypertens Res 2002; 25: 475–480.
Tseng CJ, Lin HY, Lin HC, et al: Cardiovascular effects of nitric oxide in the brain stem nuclei of rats. Hypertension 1996; 27: 36–42.
Zhang K, Mayhan WG, Patel KP : Nitric oxide within the paraventricular nucleus mediates changes in renal sympathetic nerve activity. Am J Physiol 1997; 273: 864–872.
Smith CJ, Sun D, Hoegler C, et al: Reduced gene expression of vascular endothelial NO synthase and cyclooxygenase-1 in heart failure. Circ Res 1996; 78: 58–64.
Patel KP, Zhang K, Zucker IH, et al: Decreased gene expression of neuronal nitric oxide synthase in hypothalamus and brainstem of rats in heart failure. Brain Res 1996; 734: 109–115.
Zhang K, Zucker IH, Patel KP : Altered number of diaphorase (NOS) positive neurons in the hypothalamus of rats with heart failure. Brain Res 1998; 786: 219–225.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Noda, A., Nakata, S., Koike, Y. et al. Continuous Positive Airway Pressure Improves Daytime Baroreflex Sensitivity and Nitric Oxide Production in Patients with Moderate to Severe Obstructive Sleep Apnea Syndrome. Hypertens Res 30, 669–676 (2007). https://doi.org/10.1291/hypres.30.669
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.30.669
Keywords
This article is cited by
-
Obstructive sleep apnea and non-dipper: epiphenomena or risks of Alzheimer’s disease?: a review from the HOPE Asia Network
Hypertension Research (2024)
-
Peripheral blood oxidative stress markers for obstructive sleep apnea—a meta-analysis
Sleep and Breathing (2022)
-
Possible Preventative/Rehabilitative Role of Gliflozins in OSA and T2DM. A Systematic Literature Review-Based Hypothesis
Advances in Therapy (2021)
-
The role of nitric oxide (NO) levels in patients with obstructive sleep apnea-hypopnea syndrome: a meta-analysis
Sleep and Breathing (2021)
-
Influences of obstructive sleep apnea on blood pressure variability might not be limited only nocturnally in middle-aged hypertensive males
Sleep and Breathing (2018)