Skip to main content
SpringerLink
Log in

Mechanisms Underlying Essential Hypertension: Neurogenic and Nonneurogenic Contributors

  • Chapter
  • First Online:
Hypertension and Stroke

Part of the book series: Clinical Hypertension and Vascular Diseases ((CHVD))

  • 2364 Accesses

Abstract

Stroke is the third leading cause of death in the USA and a leading cause of incapacitation, often leaving individuals permanently impaired and unable to work or live independent lives. One of the leading risk factors for stroke is hypertension, and the risk of stroke is directly proportional to the elevation and duration of high blood pressure (1–3). Furthermore, hypertension also contributes significantly to cardiovascular disease, which itself increases the risk of stroke. Despite the prevalence of hypertension, its significant negative impacts on health, and nearly a century of research, the mechanisms underlying the chronic increase in arterial pressure in most hypertensive individuals remain elusive. As initially elucidated by Guyton and others, renal factors are a prominent contributor to hypertension in many individuals, but an increasing amount of research indicates that the sympathetic nervous system and its interactions with vasoactive hormones and intracellularly generated substances also contribute to the pathogenesis of hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mvundura M, McGruder H, Khoury MJ, Valdez R, Yoon PW. Family history as a risk factor for early-onset stroke/transient ischemic attack among adults in the United States. Public Health Genomics. 23 Mar 2010;13:13–20.

    Article  Google Scholar 

  2. Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet. 7 Apr 1990;335(8693):827–38.

    Article  Google Scholar 

  3. MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 31 March 1990;335(8692):765–74.

    Article  Google Scholar 

  4. Grassi G, Quarti-Trevano F, Dell’oro R, Mancia G. Essential hypertension and the sympathetic nervous system. Neurol Sci. May 2008;29(Suppl 1):S33–6.

    Article  Google Scholar 

  5. Dampney RA, Horiuchi J, Tagawa T, Fontes MA, Potts PD, Polson JW. Medullary and supramedullary mechanisms regulating sympathetic vasomotor tone. Acta Physiol Scand. Mar 2003;177(3):209–18.

    Article  Google Scholar 

  6. Yajima Y, Ito S, Komatsu K, Tsukamoto K, Matsumoto K, Hirayama A. Enhanced response from the caudal pressor area in spontaneously hypertensive rats. Brain Res. 28 Aug 2008;1227:89–95.

    Article  CAS  PubMed  Google Scholar 

  7. Potas JR, Dampney RA. Sympathoinhibitory pathway from caudal midline medulla to RVLM is independent of baroreceptor reflex pathway. Am J Physiol Regul Integr Comp Physiol. Apr 2003;284(4):R1071–8.

    Google Scholar 

  8. Moreira TS, Takakura AC, Colombari E, Guyenet PG. Central chemoreceptors and sympathetic vasomotor outflow. J Physiol. 15 Nov 2006;577(Pt 1):369–86.

    Google Scholar 

  9. Dias AC, Vitela M, Colombari E, Mifflin SW. Nitric oxide modulation of glutamatergic, baroreflex, and cardiopulmonary transmission in the nucleus of the solitary tract. Am J Physiol Heart Circ Physiol. Jan 2005;288(1):H256–62.

    Google Scholar 

  10. Haywood JR, Mifflin SW, Craig T, Calderon A, Hensler JG, Hinojosa-Laborde C. Gamma-Aminobutyric acid (GABA)–A function and binding in the paraventricular nucleus of the hypothalamus in chronic renal-wrap hypertension. Hypertension. Feb 2001;37(2 Part 2):614–18.

    Google Scholar 

  11. Vitela M, Mifflin SW. Gamma-Aminobutyric acid (B) receptor-mediated responses in the nucleus tractus solitarius are altered in acute and chronic hypertension. Hypertension. Feb 2001;37(2 Part 2):619–22.

    Google Scholar 

  12. Bristow JD, Brown EB Jr, Cunningham DJ, Goode RC, Howson MG, Sleight P. The influence of ventilation, carbon dioxide and hypoxia on the baroreceptor reflex in man. J Physiol. Sep 1968;198(2):102passim–103p.

    Google Scholar 

  13. Cowley AW Jr, Liard JF, Guyton AC. Role of baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs. Circ Res. May 1973;32(5):564–76.

    Google Scholar 

  14. Cowley AW Jr. Long-term control of arterial blood pressure. Physiol Rev. Jan 1992;72(1):231–300.

    PubMed  Google Scholar 

  15. Thrasher TN. Arterial baroreceptor input contributes to long-term control of blood pressure. Curr Hypertens Rep. June 2006;8(3):249–54.

    Article  Google Scholar 

  16. Barrett CJ, Guild SJ, Ramchandra R, Malpas SC. Baroreceptor denervation prevents sympathoinhibition during angiotensin II-induced hypertension. Hypertension. July 2005;46(1):168–72.

    Article  Google Scholar 

  17. Lohmeier TE. The sympathetic nervous system and long-term blood pressure regulation. Am J Hypertens. June 2001;14(6 Pt 2):147S–54S.

    Google Scholar 

  18. Ramchandra R, Barrett CJ, Guild SJ, Malpas SC. Evidence of differential control of renal and lumbar sympathetic nerve activity in conscious rabbits. Am J Physiol Regul Integr Comp Physiol. Mar 2006;290(3):R701–8.

    Google Scholar 

  19. Oparil S, Chen Y-F, Berecek K, Calhoun DA, Wyss JM. The role of the central nervous system in hypertension. In: Hypertension: pathophysiology, diagnosis and management. 2nd ed. New York, NY: Raven Press; 1995. pp. 713–40.

    Google Scholar 

  20. Esler M, Straznicky N, Eikelis N, Masuo K, Lambert G, Lambert E. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension. Nov 2006;48(5):787–96.

    Article  Google Scholar 

  21. Ferguson AV, Latchford KJ, Samson WK. The paraventricular nucleus of the hypothalamus – a potential target for integrative treatment of autonomic dysfunction. Expert Opin Ther Targets. June 2008;12(6):717–27.

    Article  Google Scholar 

  22. Osborn JW, Jacob F, Hendel M, Collister JP, Clark L, Guzman PA. Effect of subfornical organ lesion on the development of mineralocorticoid-salt hypertension. Brain Res. 13 Sep 2006;1109(1):74–82.

    Article  CAS  PubMed  Google Scholar 

  23. Ployngam T, Collister JP. An intact median preoptic nucleus is necessary for chronic angiotensin II-induced hypertension. Brain Res. 8 Aug 2007;1162:69–75.

    Article  CAS  PubMed  Google Scholar 

  24. Wyss JM, Yang RH, Oparil S. Lesions of the anterior hypothalamic area increase arterial pressure in NaCl-sensitive spontaneously hypertensive rats. J Autonom Nerv Syst. 1990;31:21–30.

    Article  CAS  Google Scholar 

  25. Veerasingham SJ, Raizada MK. Brain renin-angiotensin system dysfunction in hypertension: recent advances and perspectives. Br J Pharmacol. May 2003;139(2):191–202.

    Article  CAS  PubMed  Google Scholar 

  26. Sanderford MG, Bishop VS. Central mechanisms of acute ANG II modulation of arterial baroreflex control of renal sympathetic nerve activity. Am J Physiol Heart Circ Physiol. 1 May 2002;282(5):H1592–602.

    Google Scholar 

  27. Kawano Y, Yoshida K, Matsuoka H, Omae T. Chronic effects of central and systemic administration of losartan on blood pressure and baroreceptor reflex in spontaneously hypertensive rats. Am J Hypertens. June 1994;7(6):536–42.

    Google Scholar 

  28. Schiffer S, Pummer S, Witte K, Lemmer B. Cardiovascular regulation in TGR(mREN2)27 rats: 24 h Variation in plasma catecholamines, angiotensin peptides, and telemetric heart rate variability. Chronobiol Int. May 2001;18(3):461–74.

    Article  Google Scholar 

  29. Berenguer LM, Garcia-Estan J, Ubeda M, Ortiz AJ, Quesada T. Role of renin-angiotensin system in the impairment of baroreflex control of heart rate in renal hypertension. J Hypertens. Dec 1991;9(12):1127–33.

    Google Scholar 

  30. Heesch CM, Crandall ME, Turbek JA. Converting enzyme inhibitors cause pressure-independent resetting of baroreflex control of sympathetic outflow. Am J Physiol. Apr 1996;270(4 Pt 2):R728–37.

    Google Scholar 

  31. Lantelme P, Cerutti C, Lo M, Paultre CZ, Ducher M. Mechanisms of spontaneous baroreflex impairment in lyon hypertensive rats. Am J Physiol. Sep 1998;275(3 Pt 2):R920–5.

    Google Scholar 

  32. Baltatu O, Janssen BJ, Bricca G, et al. Alterations in blood pressure and heart rate variability in transgenic rats with low brain angiotensinogen. Hypertension. Feb 2001;37(2 Part 2):408–13.

    Google Scholar 

  33. Paton JF, Waki H, Abdala AP, Dickinson J, Kasparov S. Vascular-brain signaling in hypertension: role of angiotensin II and nitric oxide. Curr Hypertens Rep. June 2007;9(3):242–7.

    Article  Google Scholar 

  34. Tan PS, Killinger S, Horiuchi J, Dampney RA. Baroreceptor reflex modulation by circulating angiotensin II is mediated by AT1 receptors in the nucleus tractus solitarius. Am J Physiol Regul Integr Comp Physiol. Dec 2007;293(6):R2267–78.

    Google Scholar 

  35. Fink GD, Bruner CA, Mangiapane ML. Area postrema is critical for angiotensin-induced hypertension in rats. Hypertension. 1 Apr 1987;9(4):355–61.

    Google Scholar 

  36. Matsumura K, Averill DB, Ferrario CM. Role of AT1 receptors in area postrema on baroreceptor reflex in spontaneously hypertensive rats. Brain Res. 11 Dec 1999;850(1–2):166–72.

    Google Scholar 

  37. Parsons KK, Coffman TM. The renin-angiotensin system: it’s all in your head. J Clin Invest. 2 Apr 2007;117(4):873–6.

    Article  Google Scholar 

  38. Davisson RL, Yang G, Beltz TG, Cassell MD, Johnson AK, Sigmund CD. The brain renin-angiotensin system contributes to the hypertension in mice containing both the human renin and human angiotensinogen transgenes. Circ Res. 16 Nov 1998;83(10):1047–58.

    Google Scholar 

  39. Sinnayah P, Lazartigues E, Sakai K, Sharma RV, Sigmund CD, Davisson RL. Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response. Circ Res. 10 Nov 2006;99(10):1125–31.

    Article  Google Scholar 

  40. Doobay MF, Talman LS, Obr TD, Tian X, Davisson RL, Lazartigues E. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. Jan 2007;292(1):R373–81.

    Google Scholar 

  41. Sakai K, Agassandian K, Morimoto S, et al. Local production of angiotensin II in the subfornical organ causes elevated drinking. J Clin Invest. Apr 2007;117(4):1088–95.

    Article  Google Scholar 

  42. Tagawa T, Dampney RA. AT(1) receptors mediate excitatory inputs to rostral ventrolateral medulla pressor neurons from hypothalamus. Hypertension. Dec 1999;34(6):1301–7.

    Google Scholar 

  43. Chen Q, Pan HL. Signaling mechanisms of angiotensin II-induced attenuation of GABAergic input to hypothalamic presympathetic neurons. J Neurophysiol. 1 May 2007;97(5):3279–87.

    Article  Google Scholar 

  44. Walsh T, Donnelly T, Lyons D. Impaired endothelial nitric oxide bioavailability: a common link between aging, hypertension, and atherogenesis? J Am Geriatr Soc. Jan 2009;57(1):140–5.

    Article  Google Scholar 

  45. Torok J. Participation of nitric oxide in different models of experimental hypertension. Physiol Res. 2008;57(6):813–25.

    Google Scholar 

  46. Pechanova O, Bernatova I, Pelouch V, Simko F. Protein remodelling of the heart in NO-deficient hypertension: the effect of captopril. J Mol Cell Cardiol. Dec 1997;29(12):3365–74.

    Article  Google Scholar 

  47. Zicha J, Dobesova Z, Kunes J. Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats. Hypertens Res. Dec 2006;29(12):1021–7.

    Article  Google Scholar 

  48. Kimura Y, Hirooka Y, Sagara Y, et al. Overexpression of inducible nitric oxide synthase in rostral ventrolateral medulla causes hypertension and sympathoexcitation via an increase in oxidative stress. Circ Res. 4 Feb 2005;96(2):252–60.

    Article  Google Scholar 

  49. Zhang F, Deng H. Kemp R et al. Decreased levels of cytochrome P450 2E1-derived eicosanoids sensitize renal arteries to constrictor agonists in spontaneously hypertensive rats. Hypertension. Jan 2005;45(1):103–8.

    Google Scholar 

  50. Zalba G, Beaumont FJ, San JG, et al. Vascular NADH/NADPH oxidase is involved in enhanced superoxide production in spontaneously hypertensive rats. Hypertension. May 2000;35(5):1055–61.

    Google Scholar 

  51. Callera GE, Tostes RC, Yogi A, Montezano AC, Touyz RM. Endothelin-1-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms. Clin Sci (Lond). Feb 2006;110(2):243–53.

    Google Scholar 

  52. Paravicini TM, Touyz RM. NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities. Diabetes Care. Feb 2008;31(Suppl 2):S170–80.

    Article  Google Scholar 

  53. Hirooka Y, Kimura Y, Nozoe M, Sagara Y, Ito K, Sunagawa K. Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats. Hypertens Res. Jan 2006;29(1):49–56.

    Article  CAS  PubMed  Google Scholar 

  54. Bolad I, Delafontaine P. Endothelial dysfunction: its role in hypertensive coronary disease. Curr Opin Cardiol. July 2005;20(4):270–4.

    Article  Google Scholar 

  55. Campese VM, Shaohua Y, Huiquin Z. Oxidative stress mediates angiotensin II-dependent stimulation of sympathetic nerve activity. Hypertension. Sep 2005;46(3):533–9.

    Article  Google Scholar 

  56. Zimmerman MC, Lazartigues E, Lang JA, et al. Superoxide mediates the actions of angiotensin II in the central nervous system. Circ Res. 29 Nov 2002;91(11):1038–45.

    Article  Google Scholar 

  57. Zimmerman MC, Lazartigues E, Sharma RV, Davisson RL. Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circ Res. 23 July 2004;95(2):210–16.

    Article  Google Scholar 

  58. Gebremedhin D, Lange AR, Lowry TF, et al. Production of 20-HETE and its role in autoregulation of cerebral blood flow. Circ Res. 7 July 2000;87(1):60–5.

    Google Scholar 

  59. Miyata N, Roman RJ. Role of 20-hydroxyeicosatetraenoic acid (20-HETE) in vascular system. J Smooth Muscle Res. Aug 2005;41(4):175–93.

    Article  Google Scholar 

  60. Capdevila JH, Falck JR, Imig JD. Roles of the cytochrome P450 arachidonic acid monooxygenases in the control of systemic blood pressure and experimental hypertension. Kidney Int. 27 June 2007;72:683–9.

    Article  Google Scholar 

  61. Alonso-Galicia M, Maier KG, Greene AS, Cowley AW Jr, Roman RJ. Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II. Am J Physiol Regul Integr Comp Physiol. July 2002;283(1):R60–8.

    Google Scholar 

  62. Moreno C, Maier KG, Hoagland KM, Yu M, Roman RJ. Abnormal pressure-natriuresis in hypertension: role of cytochrome P450 metabolites of arachidonic acid. Am J Hypertens. June 2001;14(6 Pt 2):90S–97S.

    Article  Google Scholar 

  63. Muthalif MM, Karzoun NA, Gaber L, et al. Angiotensin II-induced hypertension: contribution of Ras GTPase/mitogen-activated protein kinase and cytochrome P450 metabolites. Hypertension. Oct 2000;36(4):604–9.

    Google Scholar 

  64. Messer-Letienne I, Bernard N, Roman RJ, Sassard J, Benzoni D. 20-Hydroxyeicosatetraenoic acid and renal function in Lyon hypertensive rats. Eur J Pharmacol. 13 Aug 1999;378(3):291–7.

    Article  Google Scholar 

  65. Hoagland KM, Maier KG, Roman RJ. Contributions of 20-HETE to the antihypertensive effects of tempol in dahl salt-sensitive rats. Hypertension. Mar 2003;41(3 Pt 2):697–702.

    Article  CAS  PubMed  Google Scholar 

  66. Singh H, Schwartzman ML. Renal vascular cytochrome P450-derived eicosanoids in androgen-induced hypertension. Pharmacol Rep. Jan 2008;60(1):29–37.

    CAS  PubMed  Google Scholar 

  67. Llinas MT, Alexander BT, Capparelli MF, Carroll MA, Granger JP, Cytochrome P-450 Inhibition attenuates hypertension induced by reductions in uterine perfusion pressure in pregnant rats. Hypertension. 2 Feb 2004;43:623–8.

    Article  Google Scholar 

  68. Berezan DJ, Dunn KM, Falck JR, Davidge ST. Aging increases cytochrome P450 4A modulation of alpha1-adrenergic vasoconstriction in mesenteric arteries. J Cardiovasc Pharmacol. Mar 2008;51(3):327–30.

    Article  Google Scholar 

  69. Berezan DJ, Xu Y, Falck JR, Kundu AP, Davidge ST. Ovariectomy, but not estrogen deficiency, increases CYP4A modulation of alpha (1)-adrenergic vasoconstriction in aging female rats. Am J Hypertens. June 2008;21(6):685–90.

    Article  Google Scholar 

  70. Harder DR, Roman RJ, Gebremedhin D. Molecular mechanisms controlling nutritive blood flow: role of cytochrome P450 enzymes. Acta Physiol Scand. Apr 2000;168(4):543–9.

    Article  Google Scholar 

  71. Harder DR, Gebremedhin D, Narayanan J, et al. Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels. Am J Physiol. May 1994;266(5 Pt 2):H2098–107.

    Google Scholar 

  72. Imig JD, Zou AP.Ortiz de Montellano PR, Sui Z, Roman RJ. Cytochrome P-450 inhibitors alter afferent arteriolar responses to elevations in pressure. Am J Physiol. May 1994;266(5 Pt 2):H1879–85.

    Google Scholar 

  73. Frisbee JC, Roman RJ, Murali KU, Falck JR, Lombard JH. Altered mechanisms underlying hypoxic dilation of skeletal muscle resistance arteries of hypertensive versus normotensive Dahl rats. Microcirculation. Apr 2001;8(2):115–27.

    Google Scholar 

  74. Gordon GR, Mulligan SJ, Macvicar BA. Astrocyte control of the cerebrovasculature. Glia. Sep 2007;55(12):1214–21.

    Article  Google Scholar 

  75. Metea MR, Newman EA. Signalling within the neurovascular unit in the mammalian retina. Exp Physiol. July 2007;92(4):635–40.

    Article  Google Scholar 

  76. Pilitsis JG, Coplin WM, O’Regan MH, et al. Measurement of free fatty acids in cerebrospinal fluid from patients with hemorrhagic and ischemic stroke. Brain Res. Sep 26 2003;985(2):198–201.

    Article  CAS  PubMed  Google Scholar 

  77. Omura T, Tanaka Y, Miyata N, et al. Effect of a new inhibitor of the synthesis of 20-HETE on cerebral ischemia reperfusion injury. Stroke. May 2006;37(5):1307–13.

    Article  Google Scholar 

  78. Tanaka Y, Omura T, Fukasawa M, et al. Continuous inhibition of 20-HETE synthesis by TS-011 improves neurological and functional outcomes after transient focal cerebral ischemia in rats. Neurosci Res. Dec 2007;59(4):475–80.

    Google Scholar 

  79. Dunn KM, Renic M, Flasch AK, Harder DR, Falck J, Roman RJ. Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. Dec 2008;295(6):H2455–65.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, Luther College, Decorah, IA, USA

    Scott H. Carlson PhD

  2. Departments of Cell Biology and Medicine, University of Alabama, Birmingham, AL, USA

    J. Michael Wyss PhD

Authors
  1. Scott H. Carlson PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Michael Wyss PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Scott H. Carlson PhD .

Editor information

Editors and Affiliations

  1. College of Medicine, Dept. Neurology, University of Illinois, 912 S. Wood Street Room 855 N, Chicago, 60612, Illinois, USA

    Venkatesh Aiyagari

  2. University of Illinois, Department of Neurology and Rehabilitati, College of Medicine at Chicago, S. Wood St 912, Chicago, 60612, Illinois, USA

    Philip B. Gorelick

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Carlson, S.H., Wyss, J.M. (2011). Mechanisms Underlying Essential Hypertension: Neurogenic and Nonneurogenic Contributors. In: Aiyagari, V., Gorelick, P. (eds) Hypertension and Stroke. Clinical Hypertension and Vascular Diseases. Humana Press. https://doi.org/10.1007/978-1-60761-010-6_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-010-6_4

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-009-0

  • Online ISBN: 978-1-60761-010-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation