The Role of Central Nervous System Mechanisms in Resistant Hypertension

Current Hypertension Reports

Volumn 17, Issue 8, 2015, Pages

  Hering, Dagmara ^a   Schlaich, Markus ^a  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

Author keywords

Central sympathetic nervous system; Muscle sympathetic nerve activity; Neural reflex mechanisms; Noradrenaline spillover; Oxidative stress; Resistant hypertension; Therapeutic intervention

Indexed keywords

ANTIHYPERTENSIVE AGENT;

ADRENERGIC ACTIVITY; ADRENERGIC SYSTEM; AUTONOMIC NERVOUS SYSTEM; BAROREFLEX ACTIVATION THERAPY; BLOOD PRESSURE REGULATION; BRAIN DEPTH STIMULATION; BRAIN REGION; CARDIOVASCULAR RISK; CARDIOVASCULAR THERAPEUTIC DEVICE; CENTRAL NERVOUS SYSTEM; DEVICE THERAPY; DISEASE ASSOCIATION; DRUG TREATMENT FAILURE; HIGH RISK POPULATION; HUMAN; HYPERTENSION; KIDNEY DENERVATION; NEUROLOGIC DISEASE; NEUROVASCULAR COMPRESSION; OXIDATIVE STRESS; PRESSORECEPTOR; PROGNOSIS; RESISTANT HYPERTENSION; REVIEW; RISK REDUCTION; SIGNAL TRANSDUCTION; SLEEP DISORDERED BREATHING; BLOOD PRESSURE; INNERVATION; KIDNEY; PATHOPHYSIOLOGY; PHYSIOLOGY; VASCULARIZATION;

BLOOD PRESSURE; CENTRAL NERVOUS SYSTEM; DEEP BRAIN STIMULATION; HUMANS; HYPERTENSION; KIDNEY; OXIDATIVE STRESS;

EID: 84931262319     PISSN: 15226417     EISSN: 15343111     Source Type: Journal    
DOI: 10.1007/s11906-015-0570-0     Document Type: Review

References (64)

1. Esler M, Lambert G, Jennings G. Regional norepinephrine turnover in human hypertension. Clinical and experimental hypertension Part A. Theory Pract. 1989;11 Suppl 1:75–89. This study presents first evidence for organ-specific regional differentiation of sympathetic outflow indicating that increased NA release from the heart and kidney is pivotal in human essential hypertension.
2. Esler M. The 2009 Carl Ludwig Lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management. J Appl Physiol. 2010;108(2):227–37. doi:10.1152/japplphysiol.00832.2009.
3. Esler M, Lambert G, Jennings G. Increased regional sympathetic nervous activity in human hypertension—causes and consequences. J Hypertens. 1990;8:S53–7. The importance of increased renal NA spillover to the pathophysiology of essential hypertension.
4. Parati G, Esler M. The human sympathetic nervous system: its relevance in hypertension and heart failure. Eur Heart J. 2012;33(9):1058–U39. doi:10.1093/eurheartj/ehs041.
5. Schlaich MP, Lambert E, Kaye DM, Krozowski Z, Campbell DJ, Lambert G, et al. Sympathetic augmentation in hypertension—role of nerve firing, norepinephrine reuptake, and angiotensin neuromodulation. Hypertension. 2004;43(2):169–75. doi:10.1161/01.Hyp.0000103160.35395.9e.
6. Rumantir MS, Jennings GL, Lambert GW, Kaye DM, Seals DR, Esler MD. The ‘adrenaline hypothesis’ of hypertension revisited: evidence for adrenaline release from the heart of patients with essential hypertension. J Hypertens. 2000;18(6):717–23. doi:10.1097/00004872-200018060-00009. First study indicating augmented adrenaline release from cardiac sympathetic nerves and the relevant contribution of adrenaline co-transmission in triggering noradrenaline release in essential hypertension development.
7. Kaye DM, Lefkovits J, Jennings GL, Bergin P, Broughton A, Esler MD. Adverse consequences of high sympathetic nervous activity in the failing human heart. J Am Coll Cardiol. 1995;26(5):1257–63. doi:10.1016/0735-1097(95)00332-0. This study demonstrated that increased cardiac noradrenaline spillover predicted poor CV outcomes in heart failure patients.
8. Petersson M, Friberg P, Eisenhofer G, Lambert G, Rundqvist B. Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure. Eur Heart J. 2005;26(9):906–13. doi:10.1093/eurheartj/ehi184. This study documented the association of increased renal noradrenaline spillover and all-cause mortality and heart transplantation in heart failure patients.
9. Schlaich MP, Kaye DM, Lambert E, Sommerville M, Socratous F, Esler MD. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation. 2003;108(5):560–5. doi:10.1161/01.Cir.0000081775.72651.B6.
10. Grassi G, Seravalle G, Quarti-Trevano F, Dell'Oro R, Arenare F, Spaziani D, et al. Sympathetic and baroreflex cardiovascular control in hypertension-related left ventricular dysfunction. Hypertension. 2009;53(2):205–9. doi:10.1161/HYPERTENSIONAHA.108.121467.
11. Hering D, Kara T, Kucharska W, Somers VK, Narkiewicz K. High-normal blood pressure is associated with increased resting sympathetic activity but normal responses to stress tests. Blood Press. 2013;22(3):183–7. doi:10.3109/08037051.2012.759689.
12. Hering D, Lambert EA, Marusic P, Walton AS, Krum H, Lambert GW, et al. Substantial reduction in single sympathetic nerve firing after renal denervation in patients with resistant hypertension. Hypertension. 2013;61(2):457–+. doi:10.1161/Hypertensionaha.111.00194. First study documenting resting multi-unit and single-unit muscle sympathetic nerve activity in patients with resistant hypertension and the effect of renal denervation on sympathetic nerve firing.
13. Hering D, Lambert EA, Marusic P, Ika-Sari C, Walton AS, Krum H, et al. Renal nerve ablation reduces augmentation index in patients with resistant hypertension. J Hypertens. 2013;31(9):1893–900. doi:10.1097/Hjh.0b013e3283622e58.
14. Hering D, Marusic P, Walton AS, Lambert EA, Krum H, Narkiewicz K, et al. Sustained sympathetic and blood pressure reduction 1 year after renal denervation in patients with resistant hypertension. Hypertension. 2014;64(1):118–24. doi:10.1161/Hypertensionaha.113.03098. First study demonstrating the sustained effect of renal denervation on blood pressure and sympathetic nerve firing out to 12 months post procedure.
15. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment—a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research (Reprinted from Hypertension, vol 51, pg 1403–1419, 2008). Circulation. 2008;117(25):E510–26. doi:10.1161/Circulationaha.108.189141.
16. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281–357. doi:10.1097/01.hjh.0000431740.32696.cc.
17. Judd E, Calhoun DA. Apparent and true resistant hypertension: definition, prevalence and outcomes. J Hum Hypertens. 2014;28(8):463–8. doi:10.1038/jhh.2013.140.
18. Jannetta PJ, Segal R, Wolfson SK. Neurogenic Hypertension—etiology and surgical-treatment. 1. Observations in 53 patients. Ann Surg. 1985;201(3):391–8. doi:10.1097/00000658-198503000-00023. Study demonstrating the contribution of pulsatile compression of the nerve at the level of medulla oblongata to neurogenic hypertension and the potential for microvascular decompression in the treatment of associated hypertension.
19. Naraghi R, Gaab MR, Walter GF, Kleineberg B. Arterial hypertension and neurovascular compression at the ventrolateral medulla—a comparative microanatomical and pathological study. J Neurosurg. 1992;77(1):103–12. doi:10.3171/jns.1992.77.1.0103.
20. Jannetta PJ, Gendell HM. Clinical observations on etiology of essential hypertension. Surg Forum. 1979;30:431–2.
21. Amano M, Kubo T. Involvement of both Gaba-A and Gaba-B receptors in tonic inhibitory control of blood-pressure at the rostral ventrolateral medulla of the rat. N S Arch Pharmacol. 1993;348(2):146–53. doi:10.1007/Bf00164791.
22. Parmer RJ, Cervenka JH, Stone RA. Baroreflex sensitivity and heredity in essential hypertension. Circulation. 1992;85(2):497–503.
23. Smith JK, Barron KW. The rostral and caudal ventrolateral medulla in young spontaneously hypertensive rats. Brain Res. 1990;506(1):153–8. doi:10.1016/0006-8993(90)91213-Z.
24. Colombari E, Sato MA, Cravo SL, Bergamaschi CT, Campos RR, Lopes OU. Role of the medulla oblongata in hypertension. Hypertension. 2001;38(3):549–54.
25. Ferrier C, Jennings GL, Eisenhofer G, Lambert G, Cox HS, Kalff V, et al. Evidence for increased noradrenaline release from subcortical brain regions in essential hypertension. J Hypertens. 1993;11(11):1217–27. First study demonstrating increased brain noradrenaline turnover in the pathophysiology of human essential hypertension.
26. Lambert GW, Ferrier C, Kaye DM, Kalff V, Kelly MJ, Cox HS, et al. Monoaminergic neuronal activity in subcortical brain regions in essential hypertension. Blood Press. 1994;3(1–2):55–66.
27. Esler M, Lambert G, Vaz M, Thompson J, Kaye D, Kalff V, et al. Central nervous system monoamine neurotransmitter turnover in primary and obesity-related human hypertension. Clin Exp Hypertens. 1997;19(5–6):577–90. doi:10.3109/10641969709083171.
28. Foote SL, Bloom FE, Astonjones G. Nucleus locus ceruleus—new evidence of anatomical and physiological specificity. Physiol Rev. 1983;63(3):844–914.
29. Stella A, Zanchetti A. Functional role of renal afferents. Physiol Rev. 1991;71(3):659–82.
30. DiBona GF, Kopp UC. Neural control of renal function. Physiol Rev. 1997;77(1):75–197.
31. Campese VM, Kogosov E. Renal afferent denervation prevents hypertension in rats with chronic renal failure. Hypertension. 1995;25(4):878–82. First study demonstrating the contribution of afferent renal nerves from the failing kidney to the brain stem resulting in blood pressure elevation and sympathetic activation.
32. Converse RL, Jacobsen TN, Toto RD, Jost CMT, Cosentino F, Fouadtarazi F, et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992;327(27):1912–8. doi:10.1056/Nejm199212313272704. First study demonstrating the effect of nephrectomy on sympathetic nerve firing in chronic renal failure indicating that sympathetic excitation is associated with afferent signals arising from the failing kidney.
33. Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, et al. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002;106(15):1974–9. doi:10.1161/01.Cir.0000034043.16664.96.
34. Zazgornik J, Biesenbach G, Janko O, Gross C, Mair R, Brucke P, et al. Bilateral nephrectomy: the best, but often overlooked treatment for refractory hypertension in hemodialysis patients. Am J Hypertens. 1998;11(11):1364–70. doi:10.1016/S0895-7061(98)00154-X. First study demonstrating the beneficial effect of bilateral nephrectomy in the treatment of resistant hypertension in hemodialysis patients.
35. Fatouleh RH, Hammam E, Lundblad LC, Macey PM, McKenzie DK, Henderson LA, et al. Functional and structural changes in the brain associated with the increase in muscle sympathetic nerve activity in obstructive sleep apnoea. NeuroImage Clin. 2014;6:275–83. doi:10.1016/j.nicl.2014.08.021. First study which simultaneously assessed functional brain activity and sympathetic nerve firing in obstructive sleep apnoea.
36. Shantha GPS, Pancholy SB. Effect of renal sympathetic denervation on apnea-hypopnea index in patients with obstructive sleep apnea: a systematic review and meta-analysis. Sleep Breath. 2015;19(1):29–34. doi:10.1007/s11325-014-0991-z.
37. Krum H, Schlaich MP, Sobotka PA, Bohm M, Mahfoud F, Rocha-Singh K, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. Lancet. 2014;383(9917):622–9. doi:10.1016/S0140-6736(13)62192-3. First study demonstrating sustained blood pressure reduction out to 3 syears following renal denervation in patients with resistant hypertension.
38. Esler MD, Bohm M, Sievert H, Rump CL, Schmieder RE, Krum H, et al. Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial. Eur Heart J. 2014;35(26):1752–9. doi:10.1093/eurheartj/ehu209. First randomized-controlled study demonstrating the long-term effect of renal denervation on sustained blood pressure reduction in patients with resistant hypertension.
39. Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393–401. doi:10.1056/NEJMoa1402670. First prospective, single-blind, randomized, sham-controlled study which did not show a significant reduction in blood pressure in patients with resistant hypertension when compared to sham control.
40. Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J. 2015;36(4):219–27. doi:10.1093/eurheartj/ehu441. Post hoc analysis of the Symplicity HTN-3 trial which revealed several potential confounding factors that could explain the lack of a difference in blood pressure responses between the renal denervation and the sham control groups.
41. Schlaich MP, Bart B, Hering D, Walton A, Marusic P, Mahfoud F, et al. Feasibility of catheter-based renal nerve ablation and effects on sympathetic nerve activity and blood pressure in patients with end-stage renal disease. Int J Cardiol. 2013;168(3):2214–20. doi:10.1016/j.ijcard.2013.01.218. First pilot study demonstrating the feasibility of renal denervation in patients with end-stage renal disease with a substantial reduction in blood pressure and sympathetic activity.
42. Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD. Renal sympathetic nerve ablation for uncontrolled hypertension. N Engl J Med. 2009;361(9):932–4. doi:10.1056/Nejmc0904179. First case report of a patient with uncontrolled hypertension demonstrating a reduction in central sympathetic outflow after renal denervation indicating the potential involvement of afferent nerve fibers in sustained blood pressure reduction.
43. Lambert GW, Hering D, Esler MD, Marusic P, Lambert EA, Tanamas SK, et al. Health-related quality of life after renal denervation in patients with treatment-resistant hypertension. Hypertension. 2012;60(6):1479–84. doi:10.1161/Hypertensionaha.112.200865. First study demonstrating an improvement in several aspects of quality of life in patients with resistant hypertension following renal denervation.
44. Lenski D, Kindermann I, Lenski M, Ukena C, Bunz M, Mahfoud F, et al. Anxiety, depression, quality of life and stress in patients with resistant hypertension before and after catheter-based renal sympathetic denervation. Eurointervention. 2013;9(6):700–8. doi:10.4244/Eijv916a114.
45. Geiger H, Naraghi R, Schobel HP, Frank H, Sterzel RB, Fahlbusch R. Decrease of blood pressure by ventrolateral medullary decompression in essential hypertension. Lancet. 1998;352(9126):446–9. doi:10.1016/S0140-6736(97)11343-5.
46. Yin J, Wang WH, Zhang QB. A single microvascular decompression surgery cures a patient with trigeminal neuralgia, hemifacial spasm, tinnitus, hypertension, and paroxysmal supraventricular tachycardia caused by the compression of a vertebral artery. Neurol India. 2013;61(1):73–5. doi:10.4103/0028-3886.108016.
47. Legrady P, Voros E, Bajcsi D, Sonkodi S, Barzo P, Abraham G. Neurovascular pulsatile compression and neurosurgical decompression of the rostral ventrolateral medulla in medically resistant hypertensive patients. Kidney Blood Press Res. 2008;31(6):433–7. doi:10.1159/000195696.
48. Legrady P, Voros E, Bajcsi D, Fejes I, Barzo P, Abraham G. Observations of changes of blood pressure before and after neurosurgical decompression in hypertensive patients with different types of neurovascular compression of brain stem. Kidney Blood Press Res. 2013;37(4–5):451–7. doi:10.1159/000355725.
49. Smith PA, Meaney JFM, Graham LN, Stoker JB, Mackintosh AF, Mary DASG, et al. Relationship of neurovascular compression to central sympathetic discharge and essential hypertension. J Am Coll Cardiol. 2004;43(8):1453–8. doi:10.1016/j.jacc.2003.11.047. First study indicating that increased sympathetic nerve firing is related to neurovascular compression.
50. Sendeski MM, Consolim-Colombo FM, Leite CC, Rubira MC, Lessa P, Krieger EM. Increased sympathetic nerve activity correlates with neurovascular compression at the rostral ventrolateral medulla. Hypertension. 2006;47(5):988–95. doi:10.1161/.01.Hyp.0000214403.07762.47.
51. Frank H, Heusser K, Geiger H, Fahlbusch R, Naraghi R, Schobel HP. Temporary reduction of blood pressure and sympathetic nerve activity in hypertensive patients after microvascular decompression. Stroke. 2009;40(1):47–51. doi:10.1161/Strokeaha.108.518670.
52. Morimoto S, Aota Y, Sakuma T, Ichibangase A, Ikeda K, Sawada S, et al. Efficacy of clonidine in a patient with refractory hypertension and chronic renal failure exhibiting neurovascular compression of the rostral ventrolateral medulla. Hypertens Res. 2009;32(3):227–8. doi:10.1038/Hr.2009.1.
53. Pereira EAC, Wang SY, Paterson DJ, Stein JF, Aziz TZ, Green AL. Sustained reduction of hypertension by deep brain stimulation. J Clin Neurosci. 2010;17(1):124–7. doi:10.1016/j.jocn.2009.02.041. First case report demonstrating blood pressure reduction and pain relief following deep brain stimulation in a patient with resistant hypertension.
54. Patel NK, Javed S, Khan S, Papouchado M, Malizia AL, Pickering AE, et al. Deep brain stimulation relieves refractory hypertension. Neurology. 2011;76(4):405–7. doi:10.1212/Wnl.0b013e3182088108.
55. Sverrisdottir Y, Green A, Aziz T, Bahuri NF, Hyam J, Basnayake S et al. Effect of deep brain stimulation on sympathetic outflow in humans. Faseb J. 2014;28(1).
56. Lohmeier TE, Irwin ED, Rossing MA, Serdar DJ, Kieval RS. Prolonged activation of the baroreflex produces sustained hypotension. Hypertension. 2004;43(2):306–11. doi:10.1161/01.Hyp.00001111837.73693.9b.
57. Scheffers IJ, Kroon AA, Schmidli J, Jordan J, Tordoir JJ, Mohaupt MG, et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol. 2010;56(15):1254–8. doi:10.1016/j.jacc.2010.03.089. First study demonstrating sustained blood pressure reduction following carotid sinus baroreflex stimulation in patients with resistant hypertension.
58. Bakris GL, Nadim MK, Haller H, Lovett EG, Schafer JE, Bisognano JD. Baroreflex activation therapy provides durable benefit in patients with resistant hypertension: results of long-term follow-up in the Rheos Pivotal Trial. J Am Soc Hypertens. 2012;6(2):152–8. doi:10.1016/j.jash.2012.01.003.
59. Hoppe UC, Brandt MC, Wachter R, Beige J, Rump LC, Kroon AA, et al. Minimally invasive system for baroreflex activation therapy chronically lowers blood pressure with pacemaker-like safety profile: results from the Barostim neo trial. J Am Soc Hypertens. 2012;6(4):270–6. doi:10.1016/j.jash.2012.04.004.
60. Heusser K, Tank J, Engeli S, Diedrich A, Menne J, Eckert S, et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010;55(3):619–26. doi:10.1161/Hypertensionaha.109.140665.
61. Kishi T, Hirooka Y. Oxidative stress in the brain causes hypertension via sympathoexcitation. Frontiers in Physiology. 2012;3. doi:Unsp 335 Doi 10.3389/Fphys.2012.00335.
62. Chrysohoou C, Panagiotakos DB, Pitsavos C, Skoumas J, Economou M, Papadimitriou L, et al. The association between pre-hypertension status and oxidative stress markers related to atherosclerotic disease: the ATTICA study. Atherosclerosis. 2007;192(1):169–76. doi:10.1016/j.atherosclerosis.2006.04.030.
63. Davis JT, Pasha DN, Khandrika S, Fung MM, Milic M, O'Connor DT. Central hemodynamics in prehypertension: effect of the beta-adrenergic antagonist nebivolol. J Clin Hypertens. 2013;15(1):69–74. doi:10.1111/Jch.12031.
64. Hirooka Y, Kishi T, Ito K, Sunagawa K. Potential clinical application of recently discovered brain mechanisms involved in hypertension. Hypertension. 2013;62(6):995–1002. doi:10.1161/Hypertensionaha.113.00801.