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Neurogenic hypertension: pathophysiology, diagnosis and management

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Abstract

Discussions about the cause and treatment of essential hypertension usually focus on mechanisms such as sodium/volume and the renin–angiotensin system. Less often discussed is hypertension driven by the sympathetic nervous system, i.e., neurogenic hypertension. In this review I discuss the pathophysiology of neurogenic hypertension, the controversy of renal versus central origin, the clinical clues that suggest neurogenic hypertension, and the interventions best suited in its treatment. Neurogenic hypertension is most likely to occur in patients with labile or paroxysmal hypertension, but evidence of increased sympathetic tone also suggests a neurogenic component in hypertension in patients with severe or resistant hypertension, chronic renal disease, comorbidities associated with increased sympathetic tone, and ingestion of drugs that stimulate sympathetic tone. The importance of combined alpha- and beta-blockade in pharmacologic treatment and the status of renal denervation are discussed. Although there is much that is unclear in its pathophysiology, recognition of neurogenic hypertension is of considerable clinical importance in individualizing drug therapy and achieving blood pressure control.

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References

  1. Esler M (2000) The sympathetic system and hypertension. Am J Hypertens. 13(6 Pt 2):99S–105S. http://www.ncbi.nlm.nih.gov/pubmed/10921528

  2. Grassi G, Seravalle G, Quarti-Trevano F (2010) The “neuroadrenergic hypothesis” in hypertension: current evidence. Exp Physiol 95(5):581–586. https://doi.org/10.1113/expphysiol.2009.047381

    Article  PubMed  Google Scholar 

  3. Mancia G, Grassi G, Giannattasio C, Seravalle G (1999) Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertens (Dallas, Tex 1979) 34(4 Pt 2):724–728. http://www.ncbi.nlm.nih.gov/pubmed/10523349

  4. Rahn KH, Barenbrock M, Hausberg M (1999) The sympathetic nervous system in the pathogenesis of hypertension. J Hypertens Suppl 17(3):S11–4. http://www.ncbi.nlm.nih.gov/pubmed/10489093

  5. Grassi G (1998) Role of the sympathetic nervous system in human hypertension. J Hypertens 16(12 II):1979–1987. https://doi.org/10.1097/00004872-199816121-00019

    Article  PubMed  CAS  Google Scholar 

  6. Esler M, Lambert G, Jennings G (1989) Regional norepinephrine turnover in human hypertension. Clin Exp Hypertens A 11[Suppl 1]:75–89. http://www.ncbi.nlm.nih.gov/pubmed/2743607

  7. DeQuattro V, Chan S (1972) Raised plasma-catecholamines in some patients with primary hypertension. Lancet (London, England) 1(7755):806–809. http://www.ncbi.nlm.nih.gov/pubmed/4111575

  8. Lee D, Lu ZW, DeQuattro V (1996) Neural mechanisms in primary hypertension. Efficacy of alpha-blockade with doxazosin during stress. Am J Hypertens 9(1):47–53. http://www.ncbi.nlm.nih.gov/pubmed/8834706

  9. Mann SJ (2000) The mind/body link in essential hypertension: time for a new paradigm. Altern Ther Health Med 6(2):39–45. http://www.ncbi.nlm.nih.gov/pubmed/10710802

  10. Jorgensen RS, Johnson BT, Kolodziej ME, Schreer GE (1996) Elevated blood pressure and personality: a meta-analytic review. Psychol Bull 120:293–320. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed4&AN=8831299

  11. Suls J, Wan CK, Costa Jr PT (1995) Relationship of trait anger to resting blood pressure: a meta-analysis. Heal Psychol 14:444–456. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed3&AN=7498116

  12. Mann AH (1986) The psychological aspects of essential hypertension. J Psychosom Res 30(5):527–541. http://www.ncbi.nlm.nih.gov/pubmed/3772835

  13. Hunyor SN, Henderson RJ (1996) The role of stress management in blood pressure control: Why the promissory note has failed to deliver. J Hypertens 14:413–418. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed4&AN=1996168142

  14. Mann SJ, James GD (1998) Defensiveness and essential hypertension. J Psychosom Res 45:139–148. https://doi.org/10.1016/S0022-3999%2897%2900293-6

    Article  PubMed  CAS  Google Scholar 

  15. Johns EJ, Kopp UC, DiBona GF (2011) Neural control of renal function. Compr Physiol 1:731–767. https://doi.org/10.1002/cphy.c100043

  16. Saxena PR (1992) Interaction between the renin-angiotensin-aldosterone and sympathetic nervous systems. J Cardiovasc Pharmacol 19[Suppl 6]:S80–S88

    Article  PubMed  CAS  Google Scholar 

  17. Mancia G, Saino A (1995) Interactions between the shmpathetic nervous system and renin angiotensin system. In: Laragh JH, Brenner BM (ed) Hypertension: pathophysiology, diagnosis, and management, 2nd edn. Raven Press, New York, pp 399–407

  18. Ball SG (1989) The sympathetic nervous system and converting enzyme inhibition. J Cardiovasc Pharmacol 13[Suppl 3]:S17–21. http://www.ncbi.nlm.nih.gov/pubmed/2474095

  19. Grassi G, Turri C, Dell’Oro R, Stella ML, Bolla GB, Mancia G (1998) Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension. J Hypertens 16(12 Pt 1):1789–1796. http://www.ncbi.nlm.nih.gov/pubmed/9869013

  20. Giannattasio C, Cattaneo BM, Omboni S et al (1992) Sympathomoderating influence of benazepril in essential hypertension. J Hypertens 10(4):373–378. http://www.ncbi.nlm.nih.gov/pubmed/1316404

  21. Osborn JW, Foss JD (2017) Renal nerves and long-term control of arterial pressure. Compr Physiol 7(2):263–320. https://doi.org/10.1002/cphy.c150047

    Article  PubMed  Google Scholar 

  22. Webb DJ, Seidelin PH, Benjamin N, Collier JG, Struthers AD (1988) Sympathetically mediated vasoconstriction is augmented by angiotensin II in man. J Hypertens Suppl 6(4):S542–3. http://www.ncbi.nlm.nih.gov/pubmed/3241252

  23. Reid IA (1992) Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure. Am J Physiol Metab 262(6):E763–E778. https://doi.org/10.1152/ajpendo.1992.262.6.E763

    Article  CAS  Google Scholar 

  24. Lee CC, Sidani MA, Hogikyan RV, Supiano MA (1999) The effects of ramipril on sympathetic nervous system function in older patients with hypertension. Clin Pharmacol Ther 65(4):420–427. https://doi.org/10.1016/S0009-9236(99)70137-2

    Article  PubMed  CAS  Google Scholar 

  25. Hall JE, da Silva AA, do Carmo JM et al (2010) Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J Biol Chem 285(23):17271–17276. https://doi.org/10.1074/jbc.R110.113175

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. DeMarco VG, Aroor AR, Sowers JR (2014) The pathophysiology of hypertension in patients with obesity. Nat Rev Endocrinol 10(6):364–376. https://doi.org/10.1038/nrendo.2014.44

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Lohmeier TE, Iliescu R (2013) The sympathetic nervous system in obesity hypertension. Curr Hypertens Rep 15(4):409–416. https://doi.org/10.1007/s11906-013-0356-1

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bell BB, Rahmouni K (2016) Leptin as a mediator of obesity-induced hypertension. Curr Obes Rep 5(4):397–404. https://doi.org/10.1007/s13679-016-0231-x

    Article  PubMed  PubMed Central  Google Scholar 

  29. Seals DR, Dinenno FA (2004) Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging. Am J Physiol Heart Circ Physiol 287(5):H1895–H1905. https://doi.org/10.1152/ajpheart.00486.2004

    Article  PubMed  CAS  Google Scholar 

  30. Wofford MR, Anderson DC, Brown CA, Jones DW, Miller ME, Hall JE (2001) Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects. Am J Hypertens 14(7 Pt 1):694–698. http://www.ncbi.nlm.nih.gov/pubmed/11465655

  31. Erami C, Zhang H, Tanoue A, Tsujimoto G, Thomas SA, Faber JE (2005) Adrenergic catecholamine trophic activity contributes to flow-mediated arterial remodeling. Am J Physiol Heart Circ Physiol 289(2):H744–H753. https://doi.org/10.1152/ajpheart.00129.2005

    Article  PubMed  CAS  Google Scholar 

  32. Larsen R, Thorp A, Schlaich M (2014) Regulation of the sympathetic nervous system by the kidney. Curr Opin Nephrol Hypertens 23(1):61–68. https://doi.org/10.1097/01.mnh.0000437610.65287.db

    Article  PubMed  Google Scholar 

  33. Hurr C, Young CN (2016) Neural control of non-vasomotor organs in hypertension. Curr Hypertens Rep 18(4):30. https://doi.org/10.1007/s11906-016-0635-8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. McMaster WG, Kirabo A, Madhur MS, Harrison DG (2015) Inflammation, immunity, and hypertensive end-organ damage. Circ Res 116(6):1022–1033. https://doi.org/10.1161/CIRCRESAHA.116.303697

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Wenzel UO, Bode M, Kurts C, Ehmke H (2018) Salt, inflammation, IL-17 and hypertension. Br J Pharmacol. https://doi.org/10.1111/bph.14359

    Article  PubMed  Google Scholar 

  36. Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL (1991) Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest 87(6):2246–2252. https://doi.org/10.1172/JCI115260

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Reaven GM, Lithell H, Landsberg L (1996) Hypertension and associated metabolic abnormalities—the role of insulin resistance and the sympathoadrenal system. N Engl J Med 334(6):374–381. https://doi.org/10.1056/NEJM199602083340607

    Article  PubMed  CAS  Google Scholar 

  38. Jamerson KA, Julius S, Gudbrandsson T, Andersson O, Brant DO (1993) Reflex sympathetic activation induces acute insulin resistance in the human forearm. Hypertension 21(5):618–623. http://www.ncbi.nlm.nih.gov/pubmed/8491496

  39. Masuo K, Mikami H, Ogihara T, Tuck ML (1997) Sympathetic nerve hyperactivity precedes hyperinsulinemia and blood pressure elevation in a young, nonobese Japanese population. Am J Hypertens 10(1):77–83. http://www.ncbi.nlm.nih.gov/pubmed/9008251

  40. Anderson EA, Mark AL (1993) The vasodilator action of insulin. Implications for the insulin hypothesis of hypertension. Hypertension 21(2):136–141. http://www.ncbi.nlm.nih.gov/pubmed/8428776

  41. Marques FZ, Morris BJ (2012) Neurogenic hypertension: revelations from genome-wide gene expression profiling. Curr Hypertens Rep 14(6):485–491. https://doi.org/10.1007/s11906-012-0282-7

    Article  PubMed  CAS  Google Scholar 

  42. Jia H, Sharma P, Hopper R, Dickerson C, Lloyd DD, Brown MJ (2000) Beta2-adrenoceptor gene polymorphisms and blood pressure variations in East Anglian Caucasians. J Hypertens 18(6):687–693. http://www.ncbi.nlm.nih.gov/pubmed/10872552

  43. Bray MS, Krushkal J, Li L, et al (2000) Positional genomic analysis identifies the beta(2)-adrenergic receptor gene as a susceptibility locus for human hypertension. Circulation 101(25):2877–2882. http://www.ncbi.nlm.nih.gov/pubmed/10869257

  44. Timmermann B, Mo R, Luft FC et al (1998) β-2 Adrenoceptor genetic variation is associated with genetic predisposition to essential hypertension: the Bergen Blood Pressure Study. Kidney Int 53(6):1455–1460. https://doi.org/10.1046/j.1523-1755.1998.00926.x

    Article  PubMed  CAS  Google Scholar 

  45. Herrmann V, Büscher R, Go MM et al (2000) Beta2-adrenergic receptor polymorphisms at codon 16, cardiovascular phenotypes and essential hypertension in whites and African Americans. Am J Hypertens 13(9):1021–1026. http://www.ncbi.nlm.nih.gov/pubmed/10981553

  46. Jannetta PJ, Segal R, Wolfson SK (1985) Neurogenic hypertension: etiology and surgical treatment. I. Observations in 53 patients. Ann Surg 201(3):391–398. http://www.ncbi.nlm.nih.gov/pubmed/3977442

  47. Colón GP, Quint DJ, Dickinson LD et al (1998) Magnetic resonance evaluation of ventrolateral medullary compression in essential hypertension. J Neurosurg 88(2):226–231. https://doi.org/10.3171/jns.1998.88.2.0226

    Article  PubMed  Google Scholar 

  48. Hohenbleicher H, Schmitz SA, Koennecke H-C et al (2001) Neurovascular contact of cranial nerve IX and X root-entry zone in hypertensive patients. Hypertension 37(1):176–181. http://www.ncbi.nlm.nih.gov/pubmed/11208774

  49. Grassi G, Seravalle G, Brambilla G et al (2014) Marked sympathetic activation and baroreflex dysfunction in true resistant hypertension. Int J Cardiol 177(3):1020–1025. https://doi.org/10.1016/j.ijcard.2014.09.138

    Article  PubMed  Google Scholar 

  50. Hering D, Schlaich M (2015) The role of central nervous system mechanisms in resistant hypertension. Curr Hypertens Rep 17(8):58. https://doi.org/10.1007/s11906-015-0570-0

    Article  PubMed  Google Scholar 

  51. Ziakas A, Gossios T, Doumas M, Karali K, Megarisiotou A, Stiliadis I (2014) The pathophysiological basis of renal nerve ablation for the treatment of hypertension. Curr Vasc Pharmacol 12(1):23–29. http://www.ncbi.nlm.nih.gov/pubmed/23905601

  52. Johns EJ, Abdulla MH (2013) Renal nerves in blood pressure regulation. Curr Opin Nephrol Hypertens 22(5):504–510. https://doi.org/10.1097/MNH.0b013e3283641a89

    Article  PubMed  Google Scholar 

  53. Campese VM (2000) The kidney and the neurogenic control of blood pressure in renal disease. J Nephrol 13(3):221–224. http://www.ncbi.nlm.nih.gov/pubmed/10928299

  54. Frame AA, Carmichael CY, Wainford RD (2016) Renal afferents. Curr Hypertens Rep 18(9):69. https://doi.org/10.1007/s11906-016-0676-z

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Sica D, Bakris GL, White WB et al (2012) Blood pressure-lowering efficacy of the fixed-dose combination of azilsartan medoxomil and chlorthalidone: a factorial study. J Clin Hypertens 14(5):284–292. https://doi.org/10.1111/j.1751-7176.2012.00616.x

    Article  CAS  Google Scholar 

  56. Myers MG, Norris JW, Hachniski VC, Sole MJ. Plasma norepinephrine in stroke. Stroke 12(2):200–204. http://www.ncbi.nlm.nih.gov/pubmed/7233464

  57. Zwillich CW (1998) Sleep apnoea and autonomic function. Thorax 53[Suppl 3]:S20–4. http://www.ncbi.nlm.nih.gov/pubmed/10193356

  58. Johnson RH, Eisenhofer G, Lambie DG (1986) The effects of acute and chronic ingestion of ethanol on the autonomic nervous system. Drug Alcohol Depend 18(4):319–328. http://www.ncbi.nlm.nih.gov/pubmed/3816527

  59. Dudenbostel T, Acelajado MC, Pisoni R, Li P, Oparil S, Calhoun DA (2015) Refractory hypertension novelty and significance. Hypertension 66(1):126–133. https://doi.org/10.1161/HYPERTENSIONAHA.115.05449

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Schlaich MP, Socratous F, Hennebry S et al (2009) Sympathetic activation in chronic renal failure. J Am Soc Nephrol 20(5):933–939. https://doi.org/10.1681/ASN.2008040402

    Article  PubMed  Google Scholar 

  61. Neumann J, Ligtenberg G, Klein II, Koomans HA, Blankestijn PJ (2004) Sympathetic hyperactivity in chronic kidney disease: pathogenesis, clinical relevance, and treatment. Kidney Int 65(5):1568–1576. https://doi.org/10.1111/j.1523-1755.2004.00552.x

    Article  PubMed  Google Scholar 

  62. Hausberg M, Grassi G (2007) Mechanisms of sympathetic overactivity in patients with chronic renal failure: a role for chemoreflex activation? J Hypertens 25(1):47–49. https://doi.org/10.1097/HJH.0b013e3280119286

    Article  PubMed  CAS  Google Scholar 

  63. Campese VM, Krol E (2002) Neurogenic factors in renal hypertension. Curr Hypertens Rep 4(3):256–260. http://www.ncbi.nlm.nih.gov/pubmed/12003710

  64. Hausberg M, Kosch M, Harmelink P et al (2002) Sympathetic nerve activity in end-stage renal disease. Circulation 106(15):1974–1979. http://www.ncbi.nlm.nih.gov/pubmed/12370222

  65. Mann SJ (2009) The clinical spectrum of labile hypertension: a management dilemma. J Clin Hypertens (Greenwich) 11(9):491–497. https://doi.org/10.1111/j.1751-7176.2009.00155.x

    Article  Google Scholar 

  66. Friedman R, Schwartz JE, Schnall PL et al (2001) Psychological variables in hypertension: relationship to casual or ambulatory blood pressure in men. Psychosom Med 63(1):19–31. http://www.ncbi.nlm.nih.gov/pubmed/11211061

  67. Markovitz JH, Matthews KA, Kannel WB, Cobb JL, D’Agostino RB (1993) Psychological predictors of hypertension in the Framingham study: is there tension in hypertension? JAMA 270:2439–2443. https://doi.org/10.1001/jama.270.20.2439

    Article  PubMed  CAS  Google Scholar 

  68. Mann SJ (1999) Severe paroxysmal hypertension (Pseudopheochromocytoma): understanding the cause and treatment. Arch Intern Med. https://doi.org/10.1001/archinte.159.7.670

    Article  PubMed  Google Scholar 

  69. Mann SJ (1996) Severe paroxysmal hypertension: an autonomic syndrome and its relationship to repressed emotions. Psychosomatics 37:444–450. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed4&AN=1996270914

  70. Mann SJ (2015) Labile and paroxysmal hypertension: common clinical dilemmas in need of treatment studies. Curr Cardiol Rep 17(11):99. https://doi.org/10.1007/s11886-015-0646-0

  71. Grassi G, Seravalle G, Quarti-Trevano F et al (2008) Adrenergic, metabolic, and reflex abnormalities in reverse and extreme dipper hypertensives. Hypertension 52(5):925–931. https://doi.org/10.1161/hypertensionaha.108.116368

    Article  PubMed  CAS  Google Scholar 

  72. Mann SJ (1996) Severe paroxysmal hypertension: an automatic syndrome and its relationship to repressed emotions. Psychosomatics 37(5):444–450

  73. Pacak K, Linehan WM, Eisenhofer G, Walther MM, Goldstein DS (2001) Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med 134(4):315–329

    Article  PubMed  CAS  Google Scholar 

  74. Sharabi Y, Goldstein DS, Bentho O et al (2007) Sympathoadrenal function in patients with paroxysmal hypertension: pseudopheochromocytoma. J Hypertens 25(11):2286–2295. https://doi.org/10.1097/HJH.0b013e3282ef5fac

    Article  PubMed  CAS  Google Scholar 

  75. Mann SJ (2008) Severe paroxysmal hypertension (Pseudopheochromocytoma). Curr Hypertens Rep 10:12–18. https://doi.org/10.1007/s11906-008-0005-2

    Article  PubMed  Google Scholar 

  76. Mann S (2008) Severe paroxysmal hypertension (pseudopheochromocytoma). Curr Hypertens Rep 10(1):12–18. http://www.ncbi.nlm.nih.gov/pubmed/18367021

  77. Goldstein DS, Levinson PD, Zimlichman R, Pitterman A, Stull R, Keiser HR (1985) Clonidine suppression testing in essential hypertension. Ann Intern Med 102(1):42–49. http://www.ncbi.nlm.nih.gov/pubmed/3966744

  78. Grosse A, Bianchi JM, Díaz Puertas de Grosse CS, Iglesias GE, Coviello A (1990) Pressure responses of hypertensive patients treated with thiazides, beta blockers and clonidine during a psychological experimental stress situation. Medicina (B Aires) 50(2):141–144. http://www.ncbi.nlm.nih.gov/pubmed/1983221

  79. Hardman JG, Limbird LE, Molinoff PB, Ruddon RWGA (1996) The pharmacologic basis of therapeutics, 9th edn. McGraw Hill, New York

    Google Scholar 

  80. Lowenthal DT, Saris SD, Packer J, Haratz A, Conry K (1984) Mechanisms of action and the clinical pharmacology of beta-adrenergic blocking drugs. Am J Med 77(4A):119–127. http://www.ncbi.nlm.nih.gov/pubmed/6148890

  81. Taggart P, Carruthers M, Somerville W (1973) Electrocardiogram, plasma catecholamines and lipids, and their modification by oxyprenolol when speaking before an audience. Lancet (London, England) 2(7825):341–346. http://www.ncbi.nlm.nih.gov/pubmed/4124526

  82. Julius S (1988) The blood pressure seeking properties of the central nervous system. J Hypertens 6(3):177–185. http://www.ncbi.nlm.nih.gov/pubmed/3283225

  83. Mann SJ, Pickering TG, Alderman MH, Laragh JH (1989) Assessment of the effects of alpha- and beta-blockade in hypertensive patients who smoke cigarettes. Am J Med 86(1B):79–81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2913775

  84. Mills PJ, Dimsdale JE (1991) Cardiovascular reactivity to psychosocial stressors. A review of the effects of beta-blockade. Psychosomatics 32(2):209–220. https://doi.org/10.1016/S0033-3182(91)72094-X

    Article  PubMed  CAS  Google Scholar 

  85. Andrén L, Hansson L (1981) Circulatory effects of stress in essential hypertension. Acta Med Scand Suppl 646:69–72. http://www.ncbi.nlm.nih.gov/pubmed/7018187

  86. Ulrych M (1969) Changes of general haemodynamics during stressful mental arithmetic and non-stressing quiet conversation and modification of the latter by beta-adrenergic blockade. Clin Sci 36(3):453–461. http://www.ncbi.nlm.nih.gov/pubmed/5795235

  87. Andrén L, Hansson L, Eggertsen R, Hedner T, Karlberg BE (1983) Circulatory effects of noise. Acta Med Scand 213(1):31–35. http://www.ncbi.nlm.nih.gov/pubmed/6338682

  88. Dimsdale JE, Mills P, Ziegler M, Leitz K, Nelesen R (1992) Converting enzyme inhibition and blood pressure reactivity to psychological stressors. Hypertension 20(2):210–213. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1639462

  89. Shapiro AP (1962) Pressor responses to noxious stimuli in hypertensive patients. Effects of reserpine and chlorothiazide. Circulation 26:242–250. http://www.ncbi.nlm.nih.gov/pubmed/13911284

  90. Maconochie JG, Richards DA, Woodings EP(1977) Modification of pressor responses induced by “cold” [proceedings]. Br J Clin Pharmacol 4(3):389P. http://www.ncbi.nlm.nih.gov/pubmed/901713

  91. Pandhi P, Sharma PL, Sharma BK, Wahi PL (1986) Comparative effect of propranolol and labetalol on isometric exercise and cold stress induced increase in arterial blood pressure. Int J Clin Pharmacol Ther Toxicol 24(5):249–253. http://www.ncbi.nlm.nih.gov/pubmed/3525424

  92. Anand MP, Dattani KK, Datey KK. Effect of isometric exercise and mental stress on blood pressure—comparative effects of propranolol and labetalol. Indian Heart J 36(1):4–7. http://www.ncbi.nlm.nih.gov/pubmed/6706367

  93. Searle M, Dathan R, Dean S, Christensen CC, Westheim A (1990) Doxazosin in combination with atenolol in essential hypertension: a double-blind placebo-controlled multicentre trial. Eur J Clin Pharmacol 39(3):299–300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2147909

  94. Pool JL (1991) Combination antihypertensive therapy with terazosin and other antihypertensive agents: results of clinical trials. Am Heart J 122(3 Pt 2):926–931. http://www.ncbi.nlm.nih.gov/pubmed/1678924

  95. Holtzman JL, Kaihlanen PM, Rider JA, Lewin AJ, Spindler JS, Oberlin JA (1988) Concomitant administration of terazosin and atenolol for the treatment of essential hypertension. Arch Intern Med 148(3):539–543. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3277569

  96. Mann SJ, Gerber LM (2001) Low-dose alpha/beta blockade in the treatment of essential hypertension. Am J Hypertens 14(6 Pt 1):553–558

    Article  PubMed  CAS  Google Scholar 

  97. Dominiak P, Grobecker H (1982) Elevated plasma catecholamines in young hypertensive and hyperkinetic patients: effect of pindolol. Br J Clin Pharmacol 13[Suppl 2]:381S–390S. http://www.ncbi.nlm.nih.gov/pubmed/7104155

  98. ALLHAT Collaborative Research Group (2000) Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA 283(15):1967–1975. http://www.ncbi.nlm.nih.gov/pubmed/10789664. Accessed 20 Mar 2018

  99. Richards DA, Prichard BN (1979) Clinical pharmacology of labetalol. Br J Clin Pharmacol 8[Suppl 2]:89S–93S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=43165

  100. Morgan T (1994) Clinical pharmacokinetics and pharmacodynamics of carvedilol. Clin Pharmacokinet 26(5):335–346. https://doi.org/10.2165/00003088-199426050-00002

    Article  PubMed  CAS  Google Scholar 

  101. Frishman W (1979) Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 1. Pharmacodynamic and pharmacokinetic properties. Am Heart J 97:663–670. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed1&AN=1980067072

  102. McNeil JJ, Louis WJ (1984) Clinical pharmacokinetics of labetalol. Clin Pharmacokinet 9(2):157–167. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6370541

  103. Englert RG, Barlage U (1991) The addition of doxazosin to the treatment regimen of patients with hypertension not adequately controlled by beta-blockers. http://dx.doi.org/10.1016/0002-8703%2891%2990864-E

  104. Hering D, Marusic P, Walton AS et al (2014) Sustained sympathetic and blood pressure reduction 1 year after renal denervation in patients with resistant hypertension. Hypertension 64(1):118–124. https://doi.org/10.1161/hypertensionaha.113.03098

    Article  PubMed  CAS  Google Scholar 

  105. Hering D, Lambert EA, Marusic P et al (2013) Substantial reduction in single sympathetic nerve firing after renal denervation in patients with resistant hypertension. Hypertension 61(2):457–464. https://doi.org/10.1161/HYPERTENSIONAHA.111.00194

    Article  PubMed  CAS  Google Scholar 

  106. Bhatt DL, Kandzari DE, O’Neill WW et al (2014) A controlled trial of renal denervation for resistant hypertension. N Engl J Med 370(15):1393–1401. https://doi.org/10.1056/NEJMoa1402670

    Article  PubMed  CAS  Google Scholar 

  107. Azizi M, Sapoval M, Gosse P et al (2015) Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet (London, England) 385(9981):1957–1965. https://doi.org/10.1016/s0140-6736(14)61942-5

    Article  Google Scholar 

  108. Townsend RR, Mahfoud F, Kandzari DE et al (2017) Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet (London, England) 390(10108):2160–2170. https://doi.org/10.1016/s0140-6736(17)32281-x

    Article  Google Scholar 

  109. Davis M, Schiffrin EL, Joyal D (2014) Renal denervation therapy for resistant hypertension. Curr Treat Options Cardiovasc Med 16(12):350. https://doi.org/10.1007/s11936-014-0350-1

    Article  PubMed  Google Scholar 

  110. Mann SJ, Parikh NS (2012) A simplified mechanistic algorithm for treating resistant hypertension: efficacy in a retrospective study. J Clin Hypertens (Greenwich) 14:191–197

  111. Setaro JF, Black HR (1992) Refractory hypertension. N Engl J Med 327(8):543–547. https://doi.org/10.1056/NEJM199208203270808

    Article  PubMed  CAS  Google Scholar 

  112. Kandzari DE, Bhatt DL, Brar S et al (2015) Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J 36(4):219–227. https://doi.org/10.1093/eurheartj/ehu441

    Article  PubMed  Google Scholar 

  113. Fadl Elmula FEM, Hoffmann P, Larstorp AC et al (2014) Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension 63(5):991–999. https://doi.org/10.1161/hypertensionaha.114.03246

    Article  PubMed  CAS  Google Scholar 

  114. Maconochie JG, Richards DA, Woodings EP (1977) Modification of pressor responses induced by “cold” [proceedings]. Br J Clin Pharmacol 4(3):389P. http://www.ncbi.nlm.nih.gov/pubmed/901713

  115. Vaclavik J, Krenkova A, Kocianova E, Vaclavik T, Kamasova M, Taborsky M (2015) 7B.04: effect of sertraline in paroxysmal hypertension. J Hypertens 33(Suppl 1):e93. https://doi.org/10.1097/01.hjh.0000467601.49032.62

    Article  PubMed  Google Scholar 

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Mann, S.J. Neurogenic hypertension: pathophysiology, diagnosis and management. Clin Auton Res 28, 363–374 (2018). https://doi.org/10.1007/s10286-018-0541-z

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