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Roles of cardiovascular autonomic regulation and sleep patterns in high blood pressure induced by mild cold exposure in rats


Increased blood pressure (BP) caused by exposure to cold temperatures can partially explain the increased incidence of cardiovascular events in winter. However, the physiological mechanisms involved in cold-induced high BP are not well established. Many studies have focused on physiological responses to severe cold exposure. In this study, we aimed to perform a comprehensive analysis of cardiovascular autonomic function and sleep patterns in rats during exposure to mild cold, a condition relevant to humans in subtropical areas, to clarify the physiological mechanisms underlying mild cold-induced hypertension. BP, electroencephalography, electromyography, electrocardiography, and core body temperature were continuously recorded in normotensive Wistar-Kyoto rats over 24 h. All rats were housed in thermoregulated chambers at ambient temperatures of 23, 18, and 15 °C in a randomized crossover design. These 24-h physiological recordings either with or without sleep scoring showed that compared with the control temperature of 23 °C, the lower ambient temperatures of 18 and 15 °C not only increased BP, vascular sympathetic activity, and heart rate but also decreased overall autonomic activity, parasympathetic activity, and baroreflex sensitivity in rats. In addition, cold exposure reduced the delta power percentage and increased the incidence of interruptions during sleep. Moreover, a correlation analysis revealed that all of these cold-induced autonomic dysregulation and sleep problems were associated with elevation of BP. In conclusion, mild cold exposure elicits autonomic dysregulation and poor sleep quality, causing BP elevation, which may have critical implications for cold-related cardiovascular events.

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  1. 1.

    Wang H, Sekine M, Chen X, Kagamimori S. A study of weekly and seasonal variation of stroke onset. Int J Biometeorol. 2002;47:13–20.

    PubMed  Google Scholar 

  2. 2.

    Spencer FA, Goldberg RJ, Becker RC, Gore JM. Seasonal distribution of acute myocardial infarction in the second National Registry of Myocardial Infarction. J Am Coll Cardiol. 1998;31:1226–33.

    CAS  PubMed  Google Scholar 

  3. 3.

    Marchant B, Ranjadayalan K, Stevenson R, Wilkinson P, Timmis AD. Circadian and seasonal factors in the pathogenesis of acute myocardial infarction: the influence of environmental temperature. Br Heart J. 1993;69:385–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Brennan PJ, Greenberg G, Miall WE, Thompson SG. Seasonal variation in arterial blood pressure. Br Med J. 1982;285:919–23.

    CAS  Google Scholar 

  5. 5.

    Minami J, Ishimitsu T, Kawano Y, Matsuoka H. Seasonal variations in office and home blood pressures in hypertensive patients treated with antihypertensive drugs. Blood Press Monit. 1998;3:101–6.

    CAS  PubMed  Google Scholar 

  6. 6.

    Winnicki M, Canali C, Accurso V, Dorigatti F, Giovinazzo P, Palatini P. Relation of 24-hour ambulatory blood pressure and short-term blood pressure variability to seasonal changes in environmental temperature in stage I hypertensive subjects. Results of the Harvest Trial. Clin Exp Hypertens. 1996;18:995–1012.

    CAS  PubMed  Google Scholar 

  7. 7.

    Sega R, Cesana G, Bombelli M, Grassi G, Stella ML, Zanchetti A, et al. Seasonal variations in home and ambulatory blood pressure in the PAMELA population. Pressione Arteriose Monitorate E Loro Associazioni. J Hypertens. 1998;16:1585–92.

    CAS  PubMed  Google Scholar 

  8. 8.

    Kristal-Boneh E, Harari G, Green MS, Ribak J. Summer-winter variation in 24 h ambulatory blood pressure. Blood Press Monit. 1996;1:87–94.

    CAS  PubMed  Google Scholar 

  9. 9.

    Brook RD. The environment and blood pressure. Cardiol Clin. 2017;35:213–21.

    PubMed  Google Scholar 

  10. 10.

    Lavados PM, Olavarria VV, Hoffmeister L. Ambient temperature and stroke risk: evidence supporting a short-term effect at a population level from acute environmental exposures. Stroke. 2018;49:255–61.

    PubMed  Google Scholar 

  11. 11.

    Joyner MJ, Charkoudian N, Wallin BG. A sympathetic view of the sympathetic nervous system and human blood pressure regulation. Exp Physiol. 2008;93:715–24.

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    La Rovere MT, Pinna GD, Raczak G. Baroreflex sensitivity: measurement and clinical implications. Ann Noninvasive Electrocardiol. 2008;13:191–207.

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Kiviniemi AM, Tulppo MP, Hautala AJ, Perkiomaki JS, Ylitalo A, Kesaniemi YA, et al. Prognostic significance of impaired baroreflex sensitivity assessed from Phase IV of the Valsalva maneuver in a population-based sample of middle-aged subjects. Am J Cardiol. 2014;114:571–6.

    PubMed  Google Scholar 

  14. 14.

    Kuo TBJ, Yang CCH. Sleep-related changes in cardiovascular neural regulation in spontaneously hypertensive rats. Circulation. 2005;112:849–54.

    PubMed  Google Scholar 

  15. 15.

    Somers VK, Dyken ME, Mark AL, Abboud FM. Sympathetic-nerve activity during sleep in normal subjects. N Engl J Med. 1993;328:303–7.

    CAS  PubMed  Google Scholar 

  16. 16.

    Hirata T, Nakamura T, Kogure M, Tsuchiya N, Narita A, Miyagawa K, et al. Reduced sleep efficiency, measured using an objective device, was related to an increased prevalence of home hypertension in Japanese adults. Hypertens Res. 2020;43:23–9.

    PubMed  Google Scholar 

  17. 17.

    Stein PK, Pu Y. Heart rate variability, sleep and sleep disorders. Sleep Med Rev. 2012;16:47–66.

    PubMed  Google Scholar 

  18. 18.

    Yang YN, Tsai HL, Lin YC, Liu YP, Tung CS. Role of vasopressin V1 antagonist in the action of vasopressin on the cooling-evoked hemodynamic perturbations of rats. Neuropeptides. 2019;76:101939.

    CAS  PubMed  Google Scholar 

  19. 19.

    Hintsala HE, Kiviniemi AM, Tulppo MP, Helakari H, Rintamaki H, Mantysaari M, et al. Hypertension does not alter the increase in cardiac baroreflex sensitivity caused by moderate cold exposure. Front Physiol. 2016;7:204.

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Axsom JE, Nanavati AP, Rutishauser CA, Bonin JE, Moen JM, Lakatta EG. Acclimation to a thermoneutral environment abolishes age-associated alterations in heart rate and heart rate variability in conscious, unrestrained mice. Geroscience. 2020;42:217–32.

    PubMed  Google Scholar 

  21. 21.

    Papanek PE, Wood CE, Fregly MJ. Role of the sympathetic nervous system in cold-induced hypertension in rats. J Appl Physiol. 1991;71:300–6.

    CAS  PubMed  Google Scholar 

  22. 22.

    Stemper B, Hilz MJ, Rauhut U, Neundorfer B. Evaluation of cold face test bradycardia by means of spectral analysis. Clin Auton Res. 2002;12:78–83.

    CAS  PubMed  Google Scholar 

  23. 23.

    Krauchi K, Gasio PF, Vollenweider S, Von Arb M, Dubler B, Orgul S, et al. Cold extremities and difficulties initiating sleep: evidence of co-morbidity from a random sample of a Swiss urban population. J Sleep Res. 2008;17:420–6.

    PubMed  Google Scholar 

  24. 24.

    Okamoto-Mizuno K, Mizuno K. Effects of thermal environment on sleep and circadian rhythm. J Physiol Anthropol. 2012;31:14.

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Cerri M, Ocampo-Garces A, Amici R, Baracchi F, Capitani P, Jones CA, et al. Cold exposure and sleep in the rat: effects on sleep architecture and the electroencephalogram. Sleep. 2005;28:694–705.

    PubMed  Google Scholar 

  26. 26.

    Xie L, Liu B, Wang X, Mei M, Li M, Yu X, et al. Effects of different stresses on cardiac autonomic control and cardiovascular coupling. J Appl Physiol. 2017;122:435–45.

    PubMed  Google Scholar 

  27. 27.

    Cui J, Durand S, Crandall CG. Baroreflex control of muscle sympathetic nerve activity during skin surface cooling. J Appl Physiol. 2007;103:1284–9.

    PubMed  Google Scholar 

  28. 28.

    Okamoto-Mizuno K, Tsuzuki K, Mizuno K, Ohshiro Y. Effects of low ambient temperature on heart rate variability during sleep in humans. Eur J Appl Physiol. 2009;105:191–7.

    PubMed  Google Scholar 

  29. 29.

    Lin YK, Ho TJ, Wang YC. Mortality risk associated with temperature and prolonged temperature extremes in elderly populations in Taiwan. Environ Res. 2011;111:1156–63.

    CAS  PubMed  Google Scholar 

  30. 30.

    Kuo TBJ, Shaw FZ, Lai CJ, Yang CCH. Asymmetry in sympathetic and vagal activities during sleep-wake transitions. Sleep. 2008;31:311–20.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Li JY, Kuo TBJ, Yen JC, Tsai SC, Yang CCH. Voluntary and involuntary running in the rat show different patterns of theta rhythm, physical activity, and heart rate. J Neurophysiol. 2014;111:2061–70.

    PubMed  Google Scholar 

  32. 32.

    Kuo TBJ, Shaw FZ, Lai CJ, Lai CW, Yang CCH. Changes in sleep patterns in spontaneously hypertensive rats. Sleep. 2004;27:406–12.

    PubMed  Google Scholar 

  33. 33.

    Bjorvatn B, Fagerland S, Ursin R. EEG power densities (0.5-20 Hz) in different sleep-wake stages in rats. Physiol Behav. 1998;63:413–7.

    CAS  PubMed  Google Scholar 

  34. 34.

    Heart Rate Variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur heart J. 1996;17:354–81.

    Google Scholar 

  35. 35.

    Kuo TBJ, Yien HW, Hseu SS, Yang CC, Lin YY, Lee LC, et al. Diminished vasomotor component of systemic arterial pressure signals and baroreflex in brain death. Am J Physiol. 1997;273(3 Pt 2):H1291–8.

    CAS  PubMed  Google Scholar 

  36. 36.

    Bertinieri G, Di Rienzo M, Cavallazzi A, Ferrari AU, Pedotti A, Mancia G. Evaluation of baroreceptor reflex by blood pressure monitoring in unanesthetized cats. Am J Physiol. 1988;254(2 Pt 2):H377–83.

    CAS  PubMed  Google Scholar 

  37. 37.

    Fritsch JM, Eckberg DL, Graves LD, Wallin BG. Arterial pressure ramps provoke linear increases of heart period in humans. Am J Physiol. 1986;251(6 Pt 2):R1086–90.

    CAS  PubMed  Google Scholar 

  38. 38.

    Munakata M, Imai Y, Takagi H, Nakao M, Yamamoto M, Abe K. Altered frequency-dependent characteristics of the cardiac baroreflex in essential hypertension. J Autonomic Nerv Syst. 1994;49:33–45.

    CAS  Google Scholar 

  39. 39.

    Kuo TBJ, Lin T, Yang CCH, Li CL, Chen CF, Chou P. Effect of aging on gender differences in neural control of heart rate. Am J Physiol. 1999;277(6 Pt 2):H2233–9.

    CAS  PubMed  Google Scholar 

  40. 40.

    Wang YC, Kuo JS, Lin SZ. The effect of sphenopalatine postganglionic neurotomy on the alteration of local cerebral blood flow of normotensive and hypertensive rats in acute cold stress. Proc Natl Sci Counc Repub China B. 1998;22:122–8.

    CAS  PubMed  Google Scholar 

  41. 41.

    Cannon B, Nedergaard J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol. 2011;214(Pt 2):242–53.

    PubMed  Google Scholar 

  42. 42.

    Sanchez-Gurmaches J, Hung CM, Guertin DA. Emerging complexities in adipocyte origins and identity. Trends Cell Biol. 2016;26:313–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Szymusiak R. Body temperature and sleep. Handb Clin Neurol. 2018;156:341–51.

    PubMed  Google Scholar 

  44. 44.

    Fedecostante M, Barbatelli P, Guerra F, Espinosa E, Dessi-Fulgheri P, Sarzani R. Summer does not always mean lower: seasonality of 24 h, daytime, and night-time blood pressure. J Hypertens. 2012;30:1392–8.

    CAS  PubMed  Google Scholar 

  45. 45.

    Yamazaki F, Sone R. Thermal stress modulates arterial pressure variability and arterial baroreflex response of heart rate during head-up tilt in humans. Eur J Appl Physiol. 2001;84:350–7.

    CAS  PubMed  Google Scholar 

  46. 46.

    Mourot L, Bouhaddi M, Gandelin E, Cappelle S, Nguyen NU, Wolf JP, et al. Conditions of autonomic reciprocal interplay versus autonomic co-activation: effects on non-linear heart rate dynamics. Auton Neurosci. 2007;137:27–36.

    PubMed  Google Scholar 

  47. 47.

    Yamazaki F, Sone R. Modulation of arterial baroreflex control of heart rate by skin cooling and heating in humans. J Appl Physiol. 2000;88:393–400.

    CAS  PubMed  Google Scholar 

  48. 48.

    Staessen JA, Thijs L, Fagard R, O’Brien ET, Clement D, de Leeuw PW, et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators. JAMA. 1999;282:539–46.

    CAS  PubMed  Google Scholar 

  49. 49.

    Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46:156–61.

    CAS  PubMed  Google Scholar 

  50. 50.

    Kuo TBJ, Chen CY, Wang YP, Lan YY, Mak KH, Lee GS, et al. The role of autonomic and baroreceptor reflex control in blood pressure dipping and nondipping in rats. J Hypertens. 2014;32:806–16.

    CAS  PubMed  Google Scholar 

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This work was financially supported by a grant (109BRC-B504) from the Brain Research Center, National Yang-Ming University, from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan; a grant (10601-62-012) from Taipei City Hospital; and grants (MOST 106-2314-B-010-025 and MOST 106-2627-E-010-001) from the Ministry of Science and Technology in Taiwan. The authors received no financial support from any manufacturer. Moreover, the authors thank Ms. Pei-Chi Hsu and Mr. Chen-Wei Huang for their article production support. The authors take full responsibility for the experimental design and the collection, analysis, and interpretation of the data.

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Correspondence to Terry B. J. Kuo or Cheryl C. H. Yang.

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Chen, CW., Wu, CH., Liou, YS. et al. Roles of cardiovascular autonomic regulation and sleep patterns in high blood pressure induced by mild cold exposure in rats. Hypertens Res 44, 662–673 (2021).

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  • Baroreflex sensitivity
  • High blood pressure
  • Heart rate variability
  • Low ambient temperature
  • Sleep pattern


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