Obstructive sleep apnea (OSA) is a common disorder (~ 4%) that augments sympathetic nerve activity (SNA) and elevates blood pressure. The relationship between sympathetic vasomotor outflow and vascular responsiveness, termed sympathetic neurovascular transduction (sNVT), has been sparsely characterized in patients with OSA. Therefore, we sought to quantify spontaneous sympathetic bursts and related changes in diastolic pressure.
Twelve participants with variable severities of OSA were recruited. We collected muscle sympathetic nerve activity (MSNA) (microneurography) and beat-by-beat diastolic pressure (finger photoplethysmography) during normoxia (FiO2 = 0.21) and hyperoxia (FiO2 = 1.0) to decrease MSNA burst frequency. MSNA burst sequences (i.e. singlets, doublets, triplets and quadruplets) were identified and coupled to changes in diastolic pressure over 15 cardiac cycles as an index of sNVT. sNVT slope for each individual was calculated from the slope of the relationship between peak responses in outcome plotted against normalized burst amplitude.
sNVT slope was unchanged during hyperoxia compared to normoxia (normoxia 0.0024 ± 0.0011 Δ mmHg total activity [a.u.]−1 vs. hyperoxia 0.0029 ± 0.00098 Δ mmHg total activity [a.u.]−1; p = 0.14). sNVT slope was inversely associated with burst frequency during hyperoxia (r = −0.58; p = 0.04), but not normoxia (r = −0.11; p = 0.71). sNVT slope was inversely associated with the apnea–hypopnea index (AHI) (r = −0.62; p = 0.030), but not after age was considered.
We have demonstrated that the prevailing MSNA frequency is unmatched to the level of sNVT, and this can be altered by acute hyperoxia.
This is a preview of subscription content, access via your institution.
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
Bradley TD, Floras JS (2009) Obstructive sleep apnoea and its cardiovascular consequences. Lancet 373(9657):82–93. https://doi.org/10.1016/S0140-6736(08)61622-0
Capistrano A, Cordeiro A, Capelozza Filho L, Almeida VC, Silva PI, Martinez S, de Almeida-Pedrin RR (2015) Facial morphology and obstructive sleep apnea. Dental Press J Orthod 20(6):60–67. https://doi.org/10.1590/2177-6709.20.6.060-067.oar
Hakim F, Gozal D, Gozal L (2012) Sympathetic and catecholaminergic alterations in sleep apnea with particular emphasis on children. Front Neurol. https://doi.org/10.3389/fneur.2012.00007
Smith EG, Voyles WF, Kirby BS, Markwald RR, Dinenno FA (2007) Ageing and leg postjunctional alpha-adrenergic vasoconstrictor responsiveness in healthy men. J Physiol 582(Pt 1):63–71. https://doi.org/10.1113/jphysiol.2007.130591
Tamisier R, Tan CO, Pepin JL, Levy P, Taylor JA (2015) Blood pressure increases in OSA due to maintained neurovascular sympathetic transduction: impact of CPAP. Sleep 38(12):1973–1980. https://doi.org/10.5665/sleep.5252
Floras JS (2016) Sympathetic nervous system in patients with sleep related breathing disorders. Curr Hypertens Rev 12(1):18–26. https://doi.org/10.2174/1573402112666160114093359
Somers VK, Dyken ME, Clary MP, Abboud FM (1995) Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 96(4):1897–1904. https://doi.org/10.1172/jci118235
Taylor KS, Murai H, Millar PJ, Haruki N, Kimmerly DS, Morris BL, Tomlinson G, Bradley TD, Floras JS (2016) Arousal from sleep and sympathetic excitation during wakefulness. Hypertension 68(6):1467–1474. https://doi.org/10.1161/hypertensionaha.116.08212
Grote L, Kraiczi H, Hedner J (2000) Reduced alpha- and beta(2)-adrenergic vascular response in patients with obstructive sleep apnea. Am J Respir Crit Care Med 162(4 Pt 1):1480–1487. https://doi.org/10.1164/ajrccm.162.4.9912028
Steinback CD, Fraser GM, Usselman CW, Reyes LM, Julian CG, Stickland MK, Chari RS, Khurana R, Davidge ST, Davenport MH (2019) Blunted sympathetic neurovascular transduction during normotensive pregnancy. J Physiol 597(14):3687–3696. https://doi.org/10.1113/jp277714
Tan CO, Tamisier R, Hamner JW, Taylor JA (2013) Characterizing sympathetic neurovascular transduction in humans. PLoS ONE 8(1):e53769–e53769. https://doi.org/10.1371/journal.pone.0053769
Hissen SL, Macefield VG, Brown R, Taylor CE (2019) Sympathetic baroreflex sensitivity is inversely related to vascular transduction in men but not women. Am J Physiol Heart Circ Physiol 317(6):H1203-h1209. https://doi.org/10.1152/ajpheart.00501.2019
Briant LJ, Burchell AE, Ratcliffe LE, Charkoudian N, Nightingale AK, Paton JF, Joyner MJ, Hart EC (2016) Quantifying sympathetic neuro-haemodynamic transduction at rest in humans: insights into sex, ageing and blood pressure control. J Physiol 594(17):4753–4768. https://doi.org/10.1113/jp272167
Berthelsen LF, Fraser GM, Simpson LL, Vanden Berg ER, Busch SA, Steele AR, Meah VL, Lawley JS, Figueroa-Mujíca R, Vizcardo Galindo GA, Villafuerte FC, Gasho C, Willie CK, Tymko MM, Ainslie PN, Stembridge M, Moore JP, Steinback CD (2020) Highs and lows of sympathetic neuro-cardiovascular transduction: influence of altitude acclimatization and adaptation. Am J Physiol Heart Circ Physiol. https://doi.org/10.1152/ajpheart.00364.2020
Goyal M, Johnson J (2017) Obstructive sleep apnea diagnosis and management. Mo Med 114(2):120–124
Phillips DB, Steinback CD, Collins SE, Fuhr DP, Bryan TL, Wong EYL, Tedjasaputra V, Bhutani M, Stickland MK (2018) The carotid chemoreceptor contributes to the elevated arterial stiffness and vasoconstrictor outflow in chronic obstructive pulmonary disease. J Physiol 596(15):3233–3244. https://doi.org/10.1113/jp275762
Vranish JR, Holwerda SW, Young BE, Credeur DP, Patik JC, Barbosa TC, Keller DM, Fadel PJ (2018) Exaggerated vasoconstriction to spontaneous bursts of muscle sympathetic nerve activity in healthy young black men. Hypertension 71(1):192–198. https://doi.org/10.1161/hypertensionaha.117.10229
Fairfax ST, Holwerda SW, Credeur DP, Zuidema MY, Medley JH, Dyke PC 2nd, Wray DW, Davis MJ, Fadel PJ (2013) The role of α-adrenergic receptors in mediating beat-by-beat sympathetic vascular transduction in the forearm of resting man. J Physiol 591(14):3637–3649. https://doi.org/10.1113/jphysiol.2013.250894
Usselman CW, Skow RJ, Matenchuk BA, Chari RS, Julian CG, Stickland MK, Davenport MH, Steinback CD (2015) Sympathetic baroreflex gain in normotensive pregnant women. J Appl Physiol (1985) 119(5):468–474. https://doi.org/10.1152/japplphysiol.00131.2015
Donadio V, Liguori R, Vetrugno R, Contin M, Elam M, Wallin BG, Karlsson T, Bugiardini E, Baruzzi A, Montagna P (2007) Daytime sympathetic hyperactivity in OSAS is related to excessive daytime sleepiness. J Sleep Res 16(3):327–332. https://doi.org/10.1111/j.1365-2869.2007.00602.x
Imadojemu VA, Mawji Z, Kunselman A, Gray KS, Hogeman CS, Leuenberger UA (2007) Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy. Chest 131(5):1406–1413. https://doi.org/10.1378/chest.06-2580
Carlson JT, Hedner JA, Sellgren J, Elam M, Wallin BG (1996) Depressed baroreflex sensitivity in patients with obstructive sleep apnea. Am J Respir Crit Care Med 154(5):1490–1496. https://doi.org/10.1164/ajrccm.154.5.8912770
Ruzicka M, Knoll G, Leenen FHH, Leech J, Aaron SD, Hiremath S (2020) Effects of CPAP on blood pressure and sympathetic activity in patients with diabetes mellitus, chronic kidney disease, and resistant hypertension. CJC Open 2(4):258–264. https://doi.org/10.1016/j.cjco.2020.03.010
Fatouleh R, McKenzie DK, Macefield VG (2014) Respiratory modulation of muscle sympathetic nerve activity in obstructive sleep apnoea. Exp Physiol 99(10):1288–1298. https://doi.org/10.1113/expphysiol.2013.077511
Goya TT, Silva RF, Guerra RS, Lima MF, Barbosa ER, Cunha PJ, Lobo DM, Buchpiguel CA, Busatto-Filho G, Negrão CE, Lorenzi-Filho G, Ueno-Pardi LM (2016) Increased muscle sympathetic nerve activity and impaired executive performance capacity in obstructive sleep apnea. Sleep 39(1):25–33. https://doi.org/10.5665/sleep.5310
Narkiewicz K, Kato M, Phillips BG, Pesek CA, Davison DE, Somers VK (1999) Nocturnal continuous positive airway pressure decreases daytime sympathetic traffic in obstructive sleep apnea. Circulation 100(23):2332–2335. https://doi.org/10.1161/01.cir.100.23.2332
Narkiewicz K, van de Borne PJ, Montano N, Dyken ME, Phillips BG, Somers VK (1998) Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea. Circulation 97(10):943–945. https://doi.org/10.1161/01.cir.97.10.943
Gilmartin GS, Lynch M, Tamisier R, Weiss JW (2010) Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity. Am J Physiol Heart Circ Physiol 299(3):H925–H931. https://doi.org/10.1152/ajpheart.00253.2009
Ryan S, Ward S, Heneghan C, McNicholas WT (2007) Predictors of decreased spontaneous baroreflex sensitivity in obstructive sleep apnea syndrome. Chest 131(4):1100–1107. https://doi.org/10.1378/chest.06-2165
Kheirandish-Gozal L, Gozal D (2019) Obstructive sleep apnea and inflammation: proof of concept based on two illustrative cytokines. Int J Mol Sci. https://doi.org/10.3390/ijms20030459
Stuckless TJR, Vermeulen TD, Brown CV, Boulet LM, Shafer BM, Wakeham DJ, Steinback CD, Ayas NT, Floras JS, Foster GE (2020) Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men. J Physiol 598(3):473–487. https://doi.org/10.1113/jp278941
Narkiewicz K, van de Borne PJ, Pesek CA, Dyken ME, Montano N, Somers VK (1999) Selective potentiation of peripheral chemoreflex sensitivity in obstructive sleep apnea. Circulation 99(9):1183–1189. https://doi.org/10.1161/01.cir.99.9.1183
Kraiczi H, Hedner J, Peker Y, Carlson J (2000) Increased vasoconstrictor sensitivity in obstructive sleep apnea. J Appl Physiol 89(2):493–498. https://doi.org/10.1152/jappl.2000.89.2.493
Mills PJ, Dimsdale JE, Coy TV, Ancoli-Israel S, Clausen JL, Nelesen RA (1995) Beta 2-adrenergic receptor characteristics in sleep apnea patients. Sleep 18(1):39–42. https://doi.org/10.1093/sleep/18.1.39
Yin Q, Yang C, Wu J, Lu H, Zheng X, Zhang Y, Lv Z, Zheng X, Li Z (2016) Downregulation of β-adrenoceptors in isoproterenol-induced cardiac remodeling through HuR. PLoS ONE 11(4):e0152005–e0152005. https://doi.org/10.1371/journal.pone.0152005
Hart EC, Joyner MJ, Wallin BG, Johnson CP, Curry TB, Eisenach JH, Charkoudian N (2009) Age-related differences in the sympathetic-hemodynamic balance in men. Hypertension 54(1):127–133. https://doi.org/10.1161/hypertensionaha.109.131417
Van Guilder GP, Westby CM, Greiner JJ, Stauffer BL, DeSouza CA (2007) Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exercise. Hypertension 50(2):403–409. https://doi.org/10.1161/hypertensionaha.107.088294
Bleeke T, Zhang H, Madamanchi N, Patterson C, Faber JE (2004) Catecholamine-induced vascular wall growth is dependent on generation of reactive oxygen species. Circ Res 94(1):37–45. https://doi.org/10.1161/01.Res.0000109412.80157.7d
Montesano M, Miano S, Paolino MC, Massolo AC, Ianniello F, Forlani M, Villa MP (2010) Autonomic cardiovascular tests in children with obstructive sleep apnea syndrome. Sleep 33(10):1349–1355. https://doi.org/10.1093/sleep/33.10.1349
This research has been funded by the Natural Sciences and Engineering Research Council of Canada (NSERC; GMF RGPIN 05205 & CDS RGPIN 06637).
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
About this article
Cite this article
Steele, A.R., Berthelsen, L.F., Fraser, G.M. et al. Blunted sympathetic neurovascular transduction is associated to the severity of obstructive sleep apnea. Clin Auton Res (2021). https://doi.org/10.1007/s10286-021-00784-8
- Obstructive sleep apnea
- Muscle sympathetic nerve activity
- Sympatho-excitation activity
- Blood pressure
- Sympathetic neurovascular transduction