Neuroscience Bulletin

, Volume 35, Issue 1, pp 98–112 | Cite as

Cellular and Molecular Mechanisms Underlying Arterial Baroreceptor Remodeling in Cardiovascular Diseases and Diabetes

  • Huiyin Tu
  • Dongze Zhang
  • Yu-Long LiEmail author


Clinical trials and animal experimental studies have demonstrated an association of arterial baroreflex impairment with the prognosis and mortality of cardiovascular diseases and diabetes. As a primary part of the arterial baroreflex arc, the pressure sensitivity of arterial baroreceptors is blunted and involved in arterial baroreflex dysfunction in cardiovascular diseases and diabetes. Changes in the arterial vascular walls, mechanosensitive ion channels, and voltage-gated ion channels contribute to the attenuation of arterial baroreceptor sensitivity. Some endogenous substances (such as angiotensin II and superoxide anion) can modulate these morphological and functional alterations through intracellular signaling pathways in impaired arterial baroreceptors. Arterial baroreceptors can be considered as a potential therapeutic target to improve the prognosis of patients with cardiovascular diseases and diabetes.


Cardiovascular disease Diabetes Baroreflex Baroreceptor Vascular wall Mechanosensitive ion channels Voltage-gated ion channels Angiotensin II Superoxide Nuclear factor-kappa B 



This review was supported by the American Heart Association (0730108N) and the National Institute of Health’s National Heart, Lung, and Blood Institute (R01HL-098503 and R01HL-137832), USA.

Compliance with Ethical Standards

Conflict of interest

All authors claim that there are no conflicts of interest.


  1. 1.
    Palma JA, Benarroch EE. Neural control of the heart: recent concepts and clinical correlations. Neurology 2014, 83: 261–271.Google Scholar
  2. 2.
    Talman WT, Kelkar P. Neural control of the heart. Central and peripheral. Neurol Clin 1993, 11: 239–256.Google Scholar
  3. 3.
    Benarroch EE. The arterial baroreflex: functional organization and involvement in neurologic disease. Neurology 2008, 71: 1733–1738.Google Scholar
  4. 4.
    Zhang D, Liu J, Tu H, Muelleman RL, Cornish KG, Li YL. In vivo transfection of manganese superoxide dismutase gene or nuclear factor kappaB shRNA in nodose ganglia improves aortic baroreceptor function in heart failure rats. Hypertension 2014, 63: 88–95.Google Scholar
  5. 5.
    Zhang D, Muelleman RL, Li YL. Angiotensin II-superoxide-NFkappaB signaling and aortic baroreceptor dysfunction in chronic heart failure. Front Neurosci 2015, 9: 382.Google Scholar
  6. 6.
    Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke Statistics-2017 Update: A report from the American Heart Association. Circulation 2017, 135: e146–e603.Google Scholar
  7. 7.
    Redon J, Tellez-Plaza M, Orozco-Beltran D, Gil-Guillen V, Pita FS, Navarro-Perez J, et al. Impact of hypertension on mortality and cardiovascular disease burden in patients with cardiovascular risk factors from a general practice setting: the ESCARVAL-risk study. J Hypertens 2016, 34: 1075–1083.Google Scholar
  8. 8.
    Stokes A, Preston SH. Deaths Attributable to diabetes in the United States: Comparison of data sources and estimation approaches. PLoS One 2017, 12: e0170219.Google Scholar
  9. 9.
    Dauphinot V, Kossovsky MP, Gueyffier F, Pichot V, Gosse P, Roche F, et al. Impaired baroreflex sensitivity and the risks of new-onset ambulatory hypertension, in an elderly population-based study. Int J Cardiol 2013, 168: 4010–4014.Google Scholar
  10. 10.
    de Moura-Tonello SC, Porta A, Marchi A, de Almeida FA, Francisco CO, Rehder-Santos P, et al. Cardiovascular variability analysis and baroreflex estimation in patients with type 2 diabetes in absence of any manifest neuropathy. PLoS One 2016, 11: e0148903.Google Scholar
  11. 11.
    Li YL, Tran TP, Muelleman R, Schultz HD. Blunted excitability of aortic baroreceptor neurons in diabetic rats: involvement of hyperpolarization-activated channel. Cardiovasc Res 2008, 79: 715–721.Google Scholar
  12. 12.
    Li YL. Elevated angiotensin II in rat nodose ganglia primes diabetes-blunted arterial baroreflex sensitivity: involvement of NADPH oxidase-derived superoxide. J Diabetes Metab 2011, 2: 1000135.Google Scholar
  13. 13.
    Martiniskova Z, Kucera P, Sykora M, Kollar B, Goldenberg Z, Turcani P. Baroreflex sensitivity in patients with type I diabetes mellitus. Neuro Endocrinol Lett 2009, 30: 491–495.Google Scholar
  14. 14.
    Ruttanaumpawan P, Gilman MP, Usui K, Floras JS, Bradley TD. Sustained effect of continuous positive airway pressure on baroreflex sensitivity in congestive heart failure patients with obstructive sleep apnea. J Hypertens 2008, 26: 1163–1168.Google Scholar
  15. 15.
    Zhang D, Liu J, Zheng H, Tu H, Muelleman RL, Li YL. Effect of angiotensin II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats. J Hypertens 2015, 33: 1401–1410.Google Scholar
  16. 16.
    Fukuda K, Kanazawa H, Aizawa Y, Ardell JL, Shivkumar K. Cardiac innervation and sudden cardiac death. Circ Res 2015, 116: 2005–2019.Google Scholar
  17. 17.
    Shen MJ, Zipes DP. Role of the autonomic nervous system in modulating cardiac arrhythmias. Circ Res 2014, 114: 1004–1021.Google Scholar
  18. 18.
    Alnima T, Kroon AA, de Leeuw PW. Baroreflex activation therapy for patients with drug-resistant hypertension. Expert Rev Cardiovasc Ther 2014, 12: 955–962.Google Scholar
  19. 19.
    Chen HS, Hwu CM, Kuo BI, Chiang SC, Kwok CF, Lee SH, et al. Abnormal cardiovascular reflex tests are predictors of mortality in Type 2 diabetes mellitus. Diabet Med 2001, 18: 268–273.Google Scholar
  20. 20.
    Gronda E, Vanoli E. Autonomic modulation with baroreflex activation therapy in heart failure. Curr Heart Fail Rep 2016, 13: 273–280.Google Scholar
  21. 21.
    Sanya EO, Brown CM, Dutsch M, Zikeli U, Neundorfer B, Hilz MJ. Impaired cardiovagal and vasomotor responses to baroreceptor stimulation in type II diabetes mellitus. Eur J Clin Invest 2003, 33: 582–588.Google Scholar
  22. 22.
    Wallbach M, Lehnig LY, Schroer C, Luders S, Bohning E, Muller GA, et al. Effects of baroreflex activation therapy on ambulatory blood pressure in patients with resistant hypertension. Hypertension 2016, 67: 701–709.Google Scholar
  23. 23.
    Tu H, Zhang L, Tran TP, Muelleman RL, Li YL. Reduced expression and activation of voltage-gated sodium channels contributes to blunted baroreflex sensitivity in heart failure rats. J Neurosci Res 2010, 88: 3337–3349.Google Scholar
  24. 24.
    Madias JE. Baroreceptor dysfunction, diabetes mellitus, and takotsubo syndrome: An intricate triangle needing exploration. Int J Cardiol 2015, 184: 517–518.Google Scholar
  25. 25.
    Rowaiye OO, Jankowska EA, Ponikowska B. Baroreceptor sensitivity and diabetes mellitus. Cardiol J 2013, 20: 453–463.Google Scholar
  26. 26.
    Bechir M, Enseleit F, Chenevard R, Muntwyler J, Luscher TF, Noll G. Folic Acid improves baroreceptor sensitivity in hypertension. J Cardiovasc Pharmacol 2005, 45: 44–48.Google Scholar
  27. 27.
    Sforza E, Martin MS, Barthelemy JC, Roche F. Is there an association between altered baroreceptor sensitivity and obstructive sleep apnoea in the healthy elderly? ERJ Open Res 2016, 2:pii: 00072–2016.Google Scholar
  28. 28.
    Shimoura CG, Lincevicius GS, Nishi EE, Girardi AC, Simon KA, Bergamaschi CT, et al. Increased dietary salt changes baroreceptor sensitivity and intrarenal renin-angiotensin system in goldblatt hypertension. Am J Hypertens 2017, 30: 28–36.Google Scholar
  29. 29.
    de Leeuw PW, Bisognano JD, Bakris GL, Nadim MK, Haller H, Kroon AA. Sustained reduction of blood pressure with baroreceptor activation therapy: results of the 6-year open follow-up. Hypertension 2017, 69: 836–843.Google Scholar
  30. 30.
    Weaver FA, Abraham WT, Little WC, Butter C, Ducharme A, Halbach M, et al. Surgical experience and long-term results of baroreflex activation therapy for heart failure with reduced ejection fraction. Semin Thorac Cardiovasc Surg 2016, 28: 320–328.Google Scholar
  31. 31.
    Ben-Menachem E. Vagus nerve stimulation, side effects, and long-term safety. J Clin Neurophysiol 2001, 18: 415–418.Google Scholar
  32. 32.
    Oparil S, Schmieder RE. New approaches in the treatment of hypertension. Circ Res 2015, 116: 1074–1095.Google Scholar
  33. 33.
    Ducreux C, Reynaud JC, Puizillout JJ. Spike conduction properties of T-shaped C neurons in the rabbit nodose ganglion. Pflugers Arch 1993, 424: 238–244.Google Scholar
  34. 34.
    Kalia M, Mesulam MM. Brain stem projections of sensory and motor components of the vagus complex in the cat: I. The cervical vagus and nodose ganglion. J Comp Neurol 1980, 193: 435–465.Google Scholar
  35. 35.
    Bock P, Gorgas K. Fine structure of baroreceptor terminals in the carotid sinus of guinea pigs and mice. Cell Tissue Res 1976, 170: 95–112.Google Scholar
  36. 36.
    Abdel-Magied EM. Ultrastructure of carotid baroreceptors in the goat. Tissue Cell 1992, 24: 681–687.Google Scholar
  37. 37.
    Taha AA, Abdel-Magied EM, King AS. Ultrastructure of aortic and pulmonary baroreceptors in the domestic fowl. J Anat 1983, 137: 197–207.Google Scholar
  38. 38.
    Abdel-Magied EM, Taha AA, King AS. An ultrastructural investigation of a baroreceptor zone in the common carotid artery of the domestic fowl. J Anat 1982, 135: 463–475.Google Scholar
  39. 39.
    Kimani JK. Electron microscopic structure and innervation of the carotid baroreceptor region in the rock hyrax (Procavia capensis). J Morphol 1992, 212: 201–211.Google Scholar
  40. 40.
    Shin HS, Hulbert WC, Biggs DF. Observations on the fine structure of the baroreceptors and adrenergic innervation of the guinea-pig carotid sinus. J Morphol 1987, 194: 65–74.Google Scholar
  41. 41.
    Krauhs JM. Structure of rat aortic baroreceptors and their relationship to connective tissue. J Neurocytol 1979, 8: 401–414.Google Scholar
  42. 42.
    Aumonier FJ. Histological observations on the distribution of baroreceptors in the carotid and aortic regions of the rabbit, cat and dog. Acta Anat (Basel) 1972, 82: 1–16.Google Scholar
  43. 43.
    Bewick GS. Synaptic-like vesicles and candidate transduction channels in mechanosensory terminals. J Anat 2015, 227: 194–213.Google Scholar
  44. 44.
    Yamasaki M, Shimizu T, Miyake M, Miyamoto Y, Katsuda S, Ishi H, et al. Effects of space flight on the histological characteristics of the aortic depressor nerve in the adult rat: electron microscopic analysis. Biol Sci Space 2004, 18: 45–51.Google Scholar
  45. 45.
    Seagard JL, Hopp FA, Drummond HA, Van Wynsberghe DM. Selective contribution of two types of carotid sinus baroreceptors to the control of blood pressure. Circ Res 1993, 72: 1011–1022.Google Scholar
  46. 46.
    Thoren P, Munch PA, Brown AM. Mechanisms for activation of aortic baroreceptor C-fibres in rabbits and rats. Acta Physiol Scand 1999, 166: 167–174.Google Scholar
  47. 47.
    Czachurski J, Lackner KJ, Ockert D, Seller H. Localization of neurones with baroreceptor input in the medial solitary nucleus by means of intracellular application of horseradish peroxidase in the cat. Neurosci Lett 1982, 28: 133–137.Google Scholar
  48. 48.
    Thrasher TN. Unloading arterial baroreceptors causes neurogenic hypertension. Am J Physiol Regul Integr Comp Physiol 2002, 282: R1044–R1053.Google Scholar
  49. 49.
    Chapleau MW, Lu Y, Abboud FM. Mechanosensitive ion channels in blood pressure-sensing baroreceptor neurons. Curr Top Membr 2007, 59: 541–567.Google Scholar
  50. 50.
    Brown AM. Receptors under pressure. An update on baroreceptors. Circ Res 1980, 46: 1–10.Google Scholar
  51. 51.
    James JE, Daly MB. Comparison of the reflex vasomotor responses to separate and combined stimulation of the carotid sinus and aortic arch baroreceptors by pulsatile and non-pulsatile pressures in the dog. J Physiol 1970, 209: 257–293.Google Scholar
  52. 52.
    Dobrin PB, Canfield TR. Elastase, collagenase, and the biaxial elastic properties of dog carotid artery. Am J Physiol 1984, 247: H124–H131.Google Scholar
  53. 53.
    Andresen MC, Yang M. Arterial baroreceptor resetting: contributions of chronic and acute processes. Clin Exp Pharmacol Physiol Suppl 1989, 15: 19–30.Google Scholar
  54. 54.
    Angell James JE. The effects of altering mean pressure, pulse pressure and pulse frequency on the impulse activity in baroreceptor fibres from the aortic arch and right subclavian artery in the rabbit. J Physiol 1971, 214: 65–88.Google Scholar
  55. 55.
    Angell James JE, Daly MB. Effects of graded pulsatile pressure on the reflex vasomotor responses elicited by changes of mean pressure in the perfused carotid sinus-aortic arch regions of the dog. J Physiol 1971, 214: 51–64.Google Scholar
  56. 56.
    Feng B, Li BY, Nauman EA, Schild JH. Theoretical and electrophysiological evidence for axial loading about aortic baroreceptor nerve terminals in rats. Am J Physiol Heart Circ Physiol 2007, 293: H3659–H3672.Google Scholar
  57. 57.
    Kimani JK. Elastin and mechanoreceptor mechanisms with special reference to the mammalian carotid sinus. Ciba Found Symp 1995, 192: 215–230.Google Scholar
  58. 58.
    Rees PM. Observations on the fine structure and distribution of presumptive baroreceptor nerves at the carotid sinus. J Comp Neurol 1967, 131: 517–548.Google Scholar
  59. 59.
    Bagshaw RJ, Fischer GM. Morphology of the carotid sinus in the dog. J Appl Physiol 1971, 31: 198–202.Google Scholar
  60. 60.
    Kimani JK, Mungai JM. Observations on the structure and innervation of the presumptive carotid sinus area in the giraffe (Giraffa camelopardalis). Acta Anat (Basel) 1983, 15: 117–133.Google Scholar
  61. 61.
    Coulson WF, Weissman N, Carnes WH. Cardiovascular studies on copper–deficient swine. VII. Mechanical properties of aortic and dermal collagen. Lab Invest 1965, 14: 303–309.Google Scholar
  62. 62.
    Bronk DW, Stella G. Afferent impulses in the carotid sinus nerve. J Cell Comp Physiol 1932, 1: 113–130.Google Scholar
  63. 63.
    Thoren P, Jones JV. Characteristics of aortic baroreceptor C-fibres in the rabbit. Acta Physiol Scand 1977, 99: 448–456.Google Scholar
  64. 64.
    Yao T, Thoren P. Characteristics of brachiocephalic and carotid sinus baroreceptors with non-medullated afferents in rabbit. Acta Physiol Scand 1983, 117: 1–8.Google Scholar
  65. 65.
    Coleridge HM, Coleridge JC. Cardiovascular afferents involved in regulation of peripheral vessels. Annu Rev Physiol 1980, 42: 413–427.Google Scholar
  66. 66.
    Aars H. Relationship between aortic diameter and aortic baroreceptor activity in normal and hypertensive rabbits. Acta Physiol Scand 1969, 75: 406–414.Google Scholar
  67. 67.
    Angell–James JE, Lumley JS. The effects of carotid endarterectomy on the mechanical properties of the carotid sinus and carotid sinus nerve activity in atherosclerotic patients. Br J Surg 1974, 61: 805–10.Google Scholar
  68. 68.
    Chesterton LJ, Sigrist MK, Bennett T, Taal MW, McIntyre CW. Reduced baroreflex sensitivity is associated with increased vascular calcification and arterial stiffness. Nephrol Dial Transplant 2005, 20: 1140–1147.Google Scholar
  69. 69.
    Jensen-Urstad K, Reichard P, Jensen-Urstad M. Decreased heart rate variability in patients with type 1 diabetes mellitus is related to arterial wall stiffness. J Intern Med 1999, 245: 57–61.Google Scholar
  70. 70.
    Lage SG, Polak JF, O’Leary DH, Creager MA. Relationship of arterial compliance to baroreflex function in hypertensive patients. Am J Physiol 1993, 265: H232–H237.Google Scholar
  71. 71.
    Okada Y, Galbreath MM, Shibata S, Jarvis SS, VanGundy TB, Meier RL, et al. Relationship between sympathetic baroreflex sensitivity and arterial stiffness in elderly men and women. Hypertension 2012, 59: 98–104.Google Scholar
  72. 72.
    Tomiyama H, Matsumoto C, Kimura K, Odaira M, Shiina K, Yamashina A. Pathophysiological contribution of vascular function to baroreflex regulation in hypertension. Circ J 2014, 78: 1414–1419.Google Scholar
  73. 73.
    Andresen MC, Kuraoka S, Brown AM. Baroreceptor function and changes in strain sensitivity in normotensive and spontaneously hypertensive rats. Circ Res 1980, 47: 821–828.Google Scholar
  74. 74.
    Andresen MC. Short- and long-term determinants of baroreceptor function in aged normotensive and spontaneously hypertensive rats. Circ Res 1984, 54: 750–759.Google Scholar
  75. 75.
    Prenner SB, Chirinos JA. Arterial stiffness in diabetes mellitus. Atherosclerosis 2015, 238: 370–379.Google Scholar
  76. 76.
    de Oliveira AR, Santos PCJL, Musso MM, de Sa CR, Krieger JE, Mill JG, et al. Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population. Diabetol Metab Syndr 2013, 5: 45.Google Scholar
  77. 77.
    Yeboah K, Antwi DA, Gyan B. Arterial stiffness in nonhypertensive type 2 diabetes patients in ghana. Int J Endocrinol 2016, 2016: 6107572.Google Scholar
  78. 78.
    Chow B, Rabkin SW. The relationship between arterial stiffness and heart failure with preserved ejection fraction: a systemic meta-analysis. Heart Fail Rev 2015, 20: 291–303.Google Scholar
  79. 79.
    Marti CN, Gheorghiade M, Kalogeropoulos AP, Georgiopoulou VV, Quyyumi AA, Butler J. Endothelial dysfunction, arterial stiffness, and heart failure. J Am Coll Cardiol 2012, 60: 1455–1469.Google Scholar
  80. 80.
    Pandey A, Khan H, Newman AB, Lakatta EG, Forman DE, Butler J, et al. Arterial stiffness and risk of overall heart failure, heart failure with preserved ejection fraction, and heart failure with reduced ejection fraction: the health ABC study (Health, aging, and body composition). Hypertension 2017, 69: 267–274.Google Scholar
  81. 81.
    Liu JL, Irvine S, Reid IA, Patel KP, Zucker IH. Chronic exercise reduces sympathetic nerve activity in rabbits with pacing–induced heart failure: A role for angiotensin II. Circulation 2000, 102: 1854–1862.Google Scholar
  82. 82.
    Sechi LA, Griffin CA, Schambelan M. The cardiac renin–angiotensin system in STZ–induced diabetes. Diabetes 1994, 43: 1180–1184.Google Scholar
  83. 83.
    Catt KJ, Cran E, Zimmet PZ, Best JB, Cain MD, Coghlan JP. Angiotensin II blood–levels in human hypertension. Lancet 1971, 297: 459–464.Google Scholar
  84. 84.
    Huskova Z, Vanourkova Z, Erbanova M, Thumova M, Opocensky M, Mullins JJ, et al. Inappropriately high circulating and intrarenal angiotensin II levels during dietary salt loading exacerbate hypertension in Cyp1a1-Ren-2 transgenic rats. J Hypertens 2010, 28: 495–509.Google Scholar
  85. 85.
    Sowers JR. Hypertension, angiotensin II, and oxidative stress. N Engl J Med 2002, 346: 1999–2001.Google Scholar
  86. 86.
    van de Wal RM, Plokker HW, Lok DJ, Boomsma F, van der Horst FA, Van Veldhuisen DJ, et al. Determinants of increased angiotensin II levels in severe chronic heart failure patients despite ACE inhibition. Int J Cardiol 2006, 106: 367–372.Google Scholar
  87. 87.
    Cardin S, Li D, Thorin-Trescases N, Leung TK, Thorin E, Nattel S. Evolution of the atrial fibrillation substrate in experimental congestive heart failure: angiotensin-dependent and -independent pathways. Cardiovasc Res 2003, 60: 315–325.Google Scholar
  88. 88.
    Roig E, Perez-Villa F, Morales M, Jimenez W, Orus J, Heras M, et al. Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J 2000, 21: 53–57.Google Scholar
  89. 89.
    Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, et al. Myocardial cell death in human diabetes. Circ Res 2000, 87: 1123–1132.Google Scholar
  90. 90.
    Shimoni Y, Liu XF. Gender differences in ANG II levels and action on multiple K+ current modulation pathways in diabetic rats. Am J Physiol Heart Circ Physiol 2004, 287: H311–H319.Google Scholar
  91. 91.
    Prasad AM, Morgan DA, Nuno DW, Ketsawatsomkron P, Bair TB, Venema AN, et al. Calcium/calmodulin–dependent kinase II inhibition in smooth muscle reduces angiotensin II–induced hypertension by controlling aortic remodeling and baroreceptor function. J Am Heart Assoc 2015, 4: e001949.Google Scholar
  92. 92.
    Chapleau MW, Hajduczok G, Sharma RV, Wachtel RE, Cunningham JT, Sullivan MJ, et al. Mechanisms of baroreceptor activation. Clin Exp Hypertens 1995, 17: 1–13.Google Scholar
  93. 93.
    Cunningham JT, Wachtel RE, Abboud FM. Mechanosensitive currents in putative aortic baroreceptor neurons in vitro. J Neurophysiol 1995, 73: 2094–2098.Google Scholar
  94. 94.
    Hajduczok G, Chapleau MW, Ferlic RJ, Mao HZ, Abboud FM. Gadolinium inhibits mechanoelectrical transduction in rabbit carotid baroreceptors. Implication of stretch-activated channels. J Clin Invest 1994, 94: 2392–2396.Google Scholar
  95. 95.
    Kraske S, Cunningham JT, Hajduczok G, Chapleau MW, Abboud FM, Wachtel RE. Mechanosensitive ion channels in putative aortic baroreceptor neurons. Am J Physiol 1998, 275: H1497–H1501.Google Scholar
  96. 96.
    Sullivan MJ, Sharma RV, Wachtel RE, Chapleau MW, Waite LJ, Bhalla RC, et al. Non-voltage-gated Ca2+ influx through mechanosensitive ion channels in aortic baroreceptor neurons. Circ Res 1997, 80: 861–867.Google Scholar
  97. 97.
    Chapleau MW, Li Z, Meyrelles SS, Ma X, Abboud FM. Mechanisms determining sensitivity of baroreceptor afferents in health and disease. Ann N Y Acad Sci 2001, 940: 1–19.Google Scholar
  98. 98.
    do Carmo JM, Huber DA, Castania JA, Fazan VP, Fazan R, Jr., Salgado HC. Aortic depressor nerve function examined in diabetic rats by means of two different approaches. J Neurosci Methods 2007, 161: 17–22.Google Scholar
  99. 99.
    Doan TN, Stephans K, Ramirez AN, Glazebrook PA, Andresen MC, Kunze DL. Differential distribution and function of hyperpolarization-activated channels in sensory neurons and mechanosensitive fibers. J Neurosci 2004, 24: 3335–3343.Google Scholar
  100. 100.
    Fazan R, Jr., Ballejo G, Salgado MC, Moraes MF, Salgado HC. Heart rate variability and baroreceptor function in chronic diabetic rats. Hypertension 1997, 30: 632–635.Google Scholar
  101. 101.
    McDowell TS, Hajduczok G, Abboud FM, Chapleau MW. Baroreflex dysfunction in diabetes mellitus. II. Site of baroreflex impairment in diabetic rabbits. Am J Physiol, 266: H244–H249.Google Scholar
  102. 102.
    Reynolds PJ, Yang M, Andresen MC. Contribution of potassium channels to the discharge properties of rat aortic baroreceptor sensory endings. Brain Res 1994, 665: 115–122.Google Scholar
  103. 103.
    Reynolds PJ, Fan W, Andresen MC. Aortic baroreceptor function in long term streptozotocin diabetic rats. Soc Neurosci 1999, 16: 221.Google Scholar
  104. 104.
    Xiao L, Wu YM, Wang R, Liu YX, Wang FW, He RR. Hydrogen sulfide facilitates carotid sinus baroreceptor activity in anesthetized male rats. Chin Med J (Engl) 2007, 120: 1343–1347.Google Scholar
  105. 105.
    Zhang H, Liu YX, Wu YM, Wang ZM, He RR. Capsaicin facilitates carotid sinus baroreceptor activity in anesthetized rats. Acta Pharmacol Sin 2004, 25: 1439–1443.Google Scholar
  106. 106.
    Yang XC, Sachs F. Block of stretch-activated ion channels in Xenopus oocytes by gadolinium and calcium ions. Science 1989, 243: 1068–1071.Google Scholar
  107. 107.
    Li YL, Zhang D, Tu H, Muelleman RL. Altered ENaC is associated with aortic baroreceptor dysfunction in chronic heart failure. Am J Hypertens 2016, 29: 582–589.Google Scholar
  108. 108.
    Simon A, Shenton F, Hunter I, Banks RW, Bewick GS. Amiloride-sensitive channels are a major contributor to mechanotransduction in mammalian muscle spindles. J Physiol 2010, 588: 171–185.Google Scholar
  109. 109.
    Du S, Araki I, Mikami Y, Zakoji H, Beppu M, Yoshiyama M, et al. Amiloride-sensitive ion channels in urinary bladder epithelium involved in mechanosensory transduction by modulating stretch-evoked adenosine triphosphate release. Urology 2007, 69: 590–595.Google Scholar
  110. 110.
    Drummond HA, Gebremedhin D, Harder DR. Degenerin/epithelial Na+ channel proteins: components of a vascular mechanosensor. Hypertension 2004, 44: 643–648.Google Scholar
  111. 111.
    Chen CC, Wong CW. Neurosensory mechanotransduction through acid-sensing ion channels. J Cell Mol Med 2013, 17: 337–349.Google Scholar
  112. 112.
    Sharif–Naeini R, Dedman A, Folgering JH, Duprat F, Patel A, Nilius B, et al. TRP channels and mechanosensory transduction: insights into the arterial myogenic response. Pflugers Arch 2008, 456: 529–540.Google Scholar
  113. 113.
    Nilius B, Honore E. Sensing pressure with ion channels. Trends Neurosci 2012, 35: 477–486.Google Scholar
  114. 114.
    Lembrechts R, Pintelon I, Schnorbusch K, Timmermans JP, Adriaensen D, Brouns I. Expression of mechanogated two-pore domain potassium channels in mouse lungs: special reference to mechanosensory airway receptors. Histochem Cell Biol 2011, 136: 371–385.Google Scholar
  115. 115.
    Xu XZ. Demystifying Mechanosensitive Piezo ion channels. Neurosci Bull 2016, 32: 307–309.Google Scholar
  116. 116.
    Xiao R, Xu XZ. Mechanosensitive channels: in touch with Piezo. Curr Biol 2010, 20: R936–R938.Google Scholar
  117. 117.
    Ben-Shahar Y. Sensory functions for degenerin/epithelial sodium channels (DEG/ENaC). Adv Genet 2011, 76: 1–26.Google Scholar
  118. 118.
    Corey DP, Garcia-Anoveros J. Mechanosensation and the DEG/ENaC ion channels. Science 1996, 273: 323–324.Google Scholar
  119. 119.
    Horisberger JD. Amiloride-sensitive Na channels. Curr Opin Cell Biol 1998, 10: 443–449.Google Scholar
  120. 120.
    Kellenberger S, Schild L. Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Physiol Rev 2002, 82: 735–767.Google Scholar
  121. 121.
    Hong K, Driscoll M. A transmembrane domain of the putative channel subunit MEC-4 influences mechanotransduction and neurodegeneration in C. elegans. Nature 1994, 367: 470–473.Google Scholar
  122. 122.
    Huang M, Chalfie M. Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans. Nature 1994, 367: 467–70.Google Scholar
  123. 123.
    O’Hagan R, Chalfie M, Goodman MB. The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals. Nat Neurosci 2005, 8: 43–50.Google Scholar
  124. 124.
    Amin MS, Wang HW, Reza E, Whitman SC, Tuana BS, Leenen FH. Distribution of epithelial sodium channels and mineralocorticoid receptors in cardiovascular regulatory centers in rat brain. Am J Physiol Regul Integr Comp Physiol 2005, 289: R1787–R1797.Google Scholar
  125. 125.
    Drummond HA, Welsh MJ, Abboud FM. ENaC subunits are molecular components of the arterial baroreceptor complex. Ann N Y Acad Sci 2001, 940: 42–47.Google Scholar
  126. 126.
    Fronius M, Clauss WG. Mechano-sensitivity of ENaC: may the (shear) force be with you. Pflugers Arch 2008, 455: 775–785.Google Scholar
  127. 127.
    Ito K, Hirooka Y, Sunagawa K. Cardiac sympathetic afferent stimulation induces salt-sensitive sympathoexcitation through hypothalamic epithelial Na+ channel activation. Am J Physiol Heart Circ Physiol 2015, 308: H530–H539.Google Scholar
  128. 128.
    Krueger B, Schlotzer-Schrehardt U, Haerteis S, Zenkel M, Chankiewitz VE, Amann KU, et al. Four subunits (alphabetagammadelta) of the epithelial sodium channel (ENaC) are expressed in the human eye in various locations. Invest Ophthalmol Vis Sci 2012, 53: 596–604.Google Scholar
  129. 129.
    Loffing J, Schild L. Functional domains of the epithelial sodium channel. J Am Soc Nephrol 2005, 16: 3175–3181.Google Scholar
  130. 130.
    Hanukoglu I. ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters. FEBS J 2017, 284: 525–545.Google Scholar
  131. 131.
    Hanukoglu I, Hanukoglu A. Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases. Gene 2016, 579: 95–132.Google Scholar
  132. 132.
    Drummond HA, Jernigan NL, Grifoni SC. Sensing tension: epithelial sodium channel/acid-sensing ion channel proteins in cardiovascular homeostasis. Hypertension 2008, 51: 1265–1271.Google Scholar
  133. 133.
    Drummond HA, Price MP, Welsh MJ, Abboud FM. A molecular component of the arterial baroreceptor mechanotransducer. Neuron 1998, 21: 1435–1441.Google Scholar
  134. 134.
    Snitsarev V, Whiteis CA, Abboud FM, Chapleau MW. Mechanosensory transduction of vagal and baroreceptor afferents revealed by study of isolated nodose neurons in culture. Auton Neurosci 2002, 98: 59–63.Google Scholar
  135. 135.
    Page AJ, Brierley SM, Martin CM, Price MP, Symonds E, Butler R, et al. Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function. Gut 2005, 54: 1408–1415.Google Scholar
  136. 136.
    Price MP, McIlwrath SL, Xie J, Cheng C, Qiao J, Tarr DE, et al. The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron 2001, 32: 1071–1083.Google Scholar
  137. 137.
    Bielefeldt K, Davis BM. Differential effects of ASIC3 and TRPV1 deletion on gastroesophageal sensation in mice. Am J Physiol Gastrointest Liver Physiol 2008, 294: G130–G138.Google Scholar
  138. 138.
    Drew LJ, Rohrer DK, Price MP, Blaver KE, Cockayne DA, Cesare P, et al. Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones. J Physiol 2004, 556: 691–710.Google Scholar
  139. 139.
    Jones RC, III, Xu L, Gebhart GF. The mechanosensitivity of mouse colon afferent fibers and their sensitization by inflammatory mediators require transient receptor potential vanilloid 1 and acid-sensing ion channel 3. J Neurosci 2005, 25: 10981–10989.Google Scholar
  140. 140.
    Kang S, Jang JH, Price MP, Gautam M, Benson CJ, Gong H, et al. Simultaneous disruption of mouse ASIC1a, ASIC2 and ASIC3 genes enhances cutaneous mechanosensitivity. PLoS One 2012, 7: e35225.Google Scholar
  141. 141.
    Lin SH, Cheng YR, Banks RW, Min MY, Bewick GS, Chen CC. Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors. Nat Commun 2016, 7: 11460.Google Scholar
  142. 142.
    Page AJ, Brierley SM, Martin CM, Martinez-Salgado C, Wemmie JA, Brennan TJ, et al. The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function. Gastroenterology 2004, 127: 1739–1747.Google Scholar
  143. 143.
    Price MP, Lewin GR, McIlwrath SL, Cheng C, Xie J, Heppenstall PA, et al. The mammalian sodium channel BNC1 is required for normal touch sensation. Nature 2000, 407: 1007–1011.Google Scholar
  144. 144.
    Lu Y, Ma X, Sabharwal R, Snitsarev V, Morgan D, Rahmouni K, et al. The ion channel ASIC2 is required for baroreceptor and autonomic control of the circulation. Neuron 2009, 64: 885–897.Google Scholar
  145. 145.
    Clapham DE. TRP channels as cellular sensors. Nature 2003, 426: 517–524.Google Scholar
  146. 146.
    Desai BN, Clapham DE. TRP channels and mice deficient in TRP channels. Pflugers Arch 2005, 451: 11–18.Google Scholar
  147. 147.
    Liedtke W, Kim C. Functionality of the TRPV subfamily of TRP ion channels: add mechano–TRP and osmo–TRP to the lexicon. Cell Mol Life Sci 2005, 62: 2985–3001.Google Scholar
  148. 148.
    Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev 2007, 87: 165–217.Google Scholar
  149. 149.
    Nilius B, Owsianik G. The transient receptor potential family of ion channels. Genome Biol 2011, 12: 218–212.Google Scholar
  150. 150.
    Pedersen SF, Nilius B. Transient receptor potential channels in mechanosensing and cell volume regulation. Methods Enzymol 2007, 428: 183–207.Google Scholar
  151. 151.
    Li H. TRP channel classification. Adv Exp Med Biol 2017, 976: 1–8.Google Scholar
  152. 152.
    Lau OC, Shen B, Wong CO, Tjong YW, Lo CY, Wang HC, et al. TRPC5 channels participate in pressure-sensing in aortic baroreceptors. Nat Commun 2016, 7: 11947.Google Scholar
  153. 153.
    Sun H, Li DP, Chen SR, Hittelman WN, Pan HL. Sensing of blood pressure increase by transient receptor potential vanilloid 1 receptors on baroreceptors. J Pharmacol Exp Ther 2009, 331: 851–859.Google Scholar
  154. 154.
    Glazebrook PA, Schilling WP, Kunze DL. TRPC channels as signal transducers. Pflugers Arch 2005, 451: 125–130.Google Scholar
  155. 155.
    Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 1952, 117: 500–544.Google Scholar
  156. 156.
    Zakon HH. Adaptive evolution of voltage-gated sodium channels: the first 800 million years. Proc Natl Acad Sci U S A 2012, 109: 10619–10625.Google Scholar
  157. 157.
    Kole MH, Ilschner SU, Kampa BM, Williams SR, Ruben PC, Stuart GJ. Action potential generation requires a high sodium channel density in the axon initial segment. Nat Neurosci 2008, 11: 178–186.Google Scholar
  158. 158.
    Doan TN, Kunze DL. Contribution of the hyperpolarization-activated current to the resting membrane potential of rat nodose sensory neurons. J Physiol 1999, 514: 125–138.Google Scholar
  159. 159.
    Li BY, Glazebrook P, Kunze DL, Schild JH. KCa1.1 channel contributes to cell excitability in unmyelinated but not myelinated rat vagal afferents. Am J Physiol Cell Physiol 2011, 300: C1393–C1403.Google Scholar
  160. 160.
    Li DP, Chen SR. Nitric oxide stimulates glutamatergic synaptic inputs to baroreceptor neurons through potentiation of Cav2.2-mediated Ca(2+) currents. Neurosci Lett 2014, 567: 57–62.Google Scholar
  161. 161.
    Li Z, Lee HC, Bielefeldt K, Chapleau MW, Abboud FM. The prostacyclin analogue carbacyclin inhibits Ca(2+)-activated K+ current in aortic baroreceptor neurones of rats. J Physiol 1997, 501: 275–87.Google Scholar
  162. 162.
    Li Z, Chapleau MW, Bates JN, Bielefeldt K, Lee HC, Abboud FM. Nitric oxide as an autocrine regulator of sodium currents in baroreceptor neurons. Neuron 1998, 20: 1039–49.Google Scholar
  163. 163.
    Matsumoto S, Takahashi M, Iwasaki K, Ide R, Saiki C, Takeda M. Direct inhibition of the transient voltage-gated K(+) currents mediates the excitability of tetrodotoxin-resistant neonatal rat nodose ganglion neurons after ouabain application. Eur J Pharmacol 2011, 659: 130–138.Google Scholar
  164. 164.
    Mendelowitz D, Kunze DL. Characterization of calcium currents in aortic baroreceptor neurons. J Neurophysiol 1992, 68: 509–517.Google Scholar
  165. 165.
    Schild JH, Kunze DL. Differential distribution of voltage-gated channels in myelinated and unmyelinated baroreceptor afferents. Auton Neurosci 2012, 172: 4–12.Google Scholar
  166. 166.
    Tatalovic M, Glazebrook PA, Kunze DL. Expression of the P/Q (Cav2.1) calcium channel in nodose sensory neurons and arterial baroreceptors. Neurosci Lett 2012, 520: 38–42.Google Scholar
  167. 167.
    Wladyka CL, Feng B, Glazebrook PA, Schild JH, Kunze DL. The KCNQ/M-current modulates arterial baroreceptor function at the sensory terminal in rats. J Physiol 2008, 586: 795–802.Google Scholar
  168. 168.
    Zhang L, Tu H, Li YL. Angiotensin II enhances hyperpolarization-activated currents in rat aortic baroreceptor neurons: involvement of superoxide. Am J Physiol Cell Physiol 2010, 298: C98–C106.Google Scholar
  169. 169.
    Li YL, Zheng H. Angiotensin II-NADPH oxidase-derived superoxide mediates diabetes-attenuated cell excitability of aortic baroreceptor neurons. Am J Physiol Cell Physiol 2011, 301: C1368–C1377.Google Scholar
  170. 170.
    Liu J, Zhang L, Tu H, Li YL. Angiotensin II induces protein overexpression of hyperpolarization-activated cyclic nucleotide-gated channels in primary cultured nodose neurons. Neurosci Lett 2012, 515: 168–173.Google Scholar
  171. 171.
    Tu H, Zhang L, Tran TP, Muelleman RL, Li YL. Diabetes alters protein expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits in rat nodose ganglion cells. Neuroscience 2010, 165: 39–52.Google Scholar
  172. 172.
    Tu H, Liu J, Zhu Z, Zhang L, Pipinos II, Li YL. Mitochondria-derived superoxide and voltage-gated sodium channels in baroreceptor neurons from chronic heart-failure rats. J Neurophysiol 2012, 107: 591–602.Google Scholar
  173. 173.
    Chang W, Berta T, Kim YH, Lee S, Lee SY, Ji RR. Expression and role of voltage–gated sodium channels in human dorsal root ganglion neurons with special focus on Nav1.7, species differences, and regulation by paclitaxel. Neurosci Bull 2018, 34: 4–12.Google Scholar
  174. 174.
    Yu FH, Catterall WA. Overview of the voltage-gated sodium channel family. Genome Biol 2003, 4: 207.Google Scholar
  175. 175.
    Catterall WA, Goldin AL, Waxman SG. International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 2005, 57: 397–409.Google Scholar
  176. 176.
    Waxman SG, Dib–Hajj S, Cummins TR, Black JA. Sodium channels and pain. Proc Natl Acad Sci U S A 1999, 96: 7635–7639.Google Scholar
  177. 177.
    Cummins TR, Sheets PL, Waxman SG. The roles of sodium channels in nociception: Implications for mechanisms of pain. Pain 2007, 131: 243–257.Google Scholar
  178. 178.
    Shen W, Gill RM, Zhang JP, Jones BD, Corbly AK, Steinberg MI. Sodium channel enhancer restores baroreflex sensitivity in conscious dogs with heart failure. Am J Physiol Heart Circ Physiol 2005, 288: H1508–H1514.Google Scholar
  179. 179.
    Kang YM, Ma Y, Zheng JP, Elks C, Sriramula S, Yang ZM, et al. Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension. Cardiovasc Res 2009, 82: 503–512.Google Scholar
  180. 180.
    Li L, Xu T, Du Y, Pan D, Wu W, Zhu H, et al. Salvianolic acid A attenuates cell apoptosis, oxidative stress, Akt and NF–kappaB activation in angiotensin-II induced murine peritoneal macrophages. Curr Pharm Biotechnol 2016, 17: 283–290.Google Scholar
  181. 181.
    Rius C, Abu-Taha M, Hermenegildo C, Piqueras L, Cerda-Nicolas JM, Issekutz AC, et al. Trans- but not cis-resveratrol impairs angiotensin-II-mediated vascular inflammation through inhibition of NF-kappaB activation and peroxisome proliferator-activated receptor-gamma upregulation. J Immunol 2010, 185: 3718–3727.Google Scholar
  182. 182.
    Ziypak T, Halici Z, Alkan E, Akpinar E, Polat B, Adanur S, et al. Renoprotective effect of aliskiren on renal ischemia/reperfusion injury in rats: electron microscopy and molecular study. Ren Fail 2015, 37: 343–354.Google Scholar
  183. 183.
    Allen AM, Lewis SJ, Verberne AJ, Mendelsohn FA. Angiotensin receptors and the vagal system. Clin Exp Hypertens A 1988, 10: 1239–1249.Google Scholar
  184. 184.
    Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007, 292: C82–C97.Google Scholar
  185. 185.
    Touyz RM, Berry C. Recent advances in angiotensin II signaling. Braz J Med Biol Res 2002, 35: 1001–1015.Google Scholar
  186. 186.
    McCord JM. Human disease, free radicals, and the oxidant/antioxidant balance. Clin Biochem 1993, 26: 351–357.Google Scholar
  187. 187.
    Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 2000, 29: 222–230.Google Scholar
  188. 188.
    Adam-Vizi V, Chinopoulos C. Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci 2006, 27: 639–645.Google Scholar
  189. 189.
    Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell 2005, 120: 483–495.Google Scholar
  190. 190.
    Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2009, 417: 1–13.Google Scholar
  191. 191.
    Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003, 552: 335–344.Google Scholar
  192. 192.
    Robinson BH. The role of manganese superoxide dismutase in health and disease. J Inherit Metab Dis 1998, 21: 598–603.Google Scholar
  193. 193.
    Wallace DC. A mitochondrial paradigm for degenerative diseases and ageing. Novartis Found Symp 2001, 235: 247–263.Google Scholar
  194. 194.
    Hoffmann A, Baltimore D. Circuitry of nuclear factor kappaB signaling. Immunol Rev 2006, 210: 171–186.Google Scholar
  195. 195.
    Israel A. The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harb Perspect Biol 2010, 2: a000158.Google Scholar
  196. 196.
    Hacker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci STKE 2006, 2006: re13.Google Scholar
  197. 197.
    Kabe Y, Ando K, Hirao S, Yoshida M, Handa H. Redox regulation of NF-kappaB activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid Redox Signal 2005, 7: 395–403.Google Scholar
  198. 198.
    Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF–[kappa]B activity. Annu Rev Immunol 2000, 18: 621–663.Google Scholar
  199. 199.
    Case AJ, Li S, Basu U, Tian J, Zimmerman MC. Mitochondrial-localized NADPH oxidase 4 is a source of superoxide in angiotensin II-stimulated neurons. Am J Physiol Heart Circ Physiol 2013, 305: H19–H28.Google Scholar
  200. 200.
    Yin JX, Yang RF, Li S, Renshaw AO, Li YL, Schultz HD, et al. Mitochondria-produced superoxide mediates angiotensin II-induced inhibition of neuronal potassium current. Am J Physiol Cell Physiol 2010, 298: C857–C865.Google Scholar
  201. 201.
    Shang LL, Sanyal S, Pfahnl AE, Jiao Z, Allen J, Liu H, et al. NF-kappaB-dependent transcriptional regulation of the cardiac scn5a sodium channel by angiotensin II. Am J Physiol Cell Physiol 2008, 294: C372–C379.Google Scholar
  202. 202.
    Brown HF, DiFrancesco D, Noble SJ. How does adrenaline accelerate the heart? Nature 1979, 280: 235–236.Google Scholar
  203. 203.
    Ishii TM, Takano M, Xie LH, Noma A, Ohmori H. Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node. J Biol Chem 1999, 274: 12835–12839.Google Scholar
  204. 204.
    Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M. A family of hyperpolarization-activated mammalian cation channels. Nature 1998, 393: 587–591.Google Scholar
  205. 205.
    Noma A, Irisawa H. Membrane currents in the rabbit sinoatrial node cell as studied by the double microelectrode method. Pflugers Arch 1976, 364: 45–52.Google Scholar
  206. 206.
    Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, et al. Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. Cell 1998, 93: 717–729.Google Scholar
  207. 207.
    Vaccari T, Moroni A, Rocchi M, Gorza L, Bianchi ME, Beltrame M, et al. The human gene coding for HCN2, a pacemaker channel of the heart. Biochim Biophys Acta 1999, 1446: 419–425.Google Scholar
  208. 208.
    DiFrancesco D. Pacemaker mechanisms in cardiac tissue. Annu Rev Physiol 1993, 55: 455–472.Google Scholar
  209. 209.
    Kaupp UB, Seifert R. Molecular diversity of pacemaker ion channels. Annu Rev Physiol 2001, 63: 235–257.Google Scholar
  210. 210.
    Notomi T, Shigemoto R. Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. J Comp Neurol 2004, 471: 241–276.Google Scholar
  211. 211.
    Pape HC. Queer current and pacemaker: the hyperpolarization-activated cation current in neurons. Annu Rev Physiol 1996, 58: 299–327.Google Scholar
  212. 212.
    Robinson RB, Siegelbaum SA. Hyperpolarization-activated cation currents: from molecules to physiological function. Annu Rev Physiol 2003, 65: 453–480.Google Scholar
  213. 213.
    Widdop RE, Krstew E, Jarrott B. Electrophysiological responses of angiotensin peptides on the rat isolated nodose ganglion. Clin Exp Hypertens A 1992, 14: 597–613.Google Scholar
  214. 214.
    Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000, 86: 494–501.Google Scholar
  215. 215.
    Cifuentes ME, Rey FE, Carretero OA, Pagano PJ. Upregulation of p67(phox) and gp91(phox) in aortas from angiotensin II-infused mice. Am J Physiol Heart Circ Physiol 2000, 279: H2234–H2240.Google Scholar
  216. 216.
    Franco MC, Akamine EH, Di Marco GS, Casarini DE, Fortes ZB, Tostes RC, et al. NADPH oxidase and enhanced superoxide generation in intrauterine undernourished rats: involvement of the renin–angiotensin system. Cardiovasc Res 2003, 59: 767–775.Google Scholar
  217. 217.
    Gao L, Wang W, Li YL, Schultz HD, Liu D, Cornish KG, et al. Superoxide mediates sympathoexcitation in heart failure: roles of angiotensin II and NAD(P)H oxidase. Circ Res 2004, 95: 937–944.Google Scholar
  218. 218.
    Li YL, Gao L, Zucker IH, Schultz HD. NADPH oxidase-derived superoxide anion mediates angiotensin II-enhanced carotid body chemoreceptor sensitivity in heart failure rabbits. Cardiovasc Res 2007, 75: 546–554.Google Scholar
  219. 219.
    Schieffer B, Luchtefeld M, Braun S, Hilfiker A, Hilfiker-Kleiner D, Drexler H. Role of NAD(P)H oxidase in angiotensin II-induced JAK/STAT signaling and cytokine induction. Circ Res 2000, 87: 1195–1201.Google Scholar

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© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Emergency MedicineUniversity of Nebraska Medical CenterOmahaUSA

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