Skip to main content
SpringerLink
Log in

Mechanisms Underlying Essential Hypertension: Neurogenic and Non-neurogenic Contributors

  • Chapter
  • First Online:
Hypertension and Stroke

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

  • 3145 Accesses

Abstract

Stroke is the fourth 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 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover 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. 2010;13:13–20.

    Article  PubMed  Google Scholar 

  2. Collins R, Peto R, Godwin J, MacMahon S. Blood pressure and coronary heart disease. Lancet. 1990;336:370–1.

    Article  CAS  PubMed  Google Scholar 

  3. MacMahon S, 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. 1990;335:765–74.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  5. Guyenet PG. The sympathetic control of blood pressure. Nat Rev Neurosci. 2006;7:335–46.

    Article  CAS  PubMed  Google Scholar 

  6. Dampney RA, et al. Medullary and supramedullary mechanisms regulating sympathetic vasomotor tone. Acta Physiol Scand. 2003;177:209–18.

    Article  CAS  PubMed  Google Scholar 

  7. Kumagai H, et al. Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure. Hypertens Res. 2012;35:132–41.

    Article  CAS  PubMed  Google Scholar 

  8. Sved AF, Ito S, Madden CJ, Stocker SD, Yajima Y. Excitatory inputs to the RVLM in the context of the baroreceptor reflex. Ann N Y Acad Sci. 2001;940:247–58.

    Article  CAS  PubMed  Google Scholar 

  9. Yajima Y, et al. Enhanced response from the caudal pressor area in spontaneously hypertensive rats. Brain Res. 2008;1227:89–95.

    Article  CAS  PubMed  Google Scholar 

  10. 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. 2003;284:R1071–8.

    Article  CAS  PubMed  Google Scholar 

  11. Moreira TS, Takakura AC, Colombari E, Guyenet PG. Central chemoreceptors and sympathetic vasomotor outflow. J Physiol. 2006;577:369–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Simmonds SS, Lay J, Stocker SD. Dietary salt intake exaggerates sympathetic reflexes and increases blood pressure variability in normotensive rats. Hypertension. 2014;64:583–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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. 2005;288:H256–62.

    Article  CAS  PubMed  Google Scholar 

  14. Haywood JR, et al. gamma-Aminobutyric acid (GABA)—a function and binding in the paraventricular nucleus of the hypothalamus in chronic renal-wrap hypertension. Hypertension. 2001;37:614–8.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Pires NM, et al. Blood pressure decrease in spontaneously hypertensive rats following renal denervation or dopamine beta-hydroxylase inhibition with etamicastat. Hypertens Res. 2015;38:605–12.

    Article  CAS  PubMed  Google Scholar 

  17. Briasoulis A, Bakris GL. A clinician’s perspective of the role of renal sympathetic nerves in hypertension. Front Physiol. 2015;6:75.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Khan SA, et al. Obesity depresses baroreflex control of renal sympathetic nerve activity and heart rate in Sprague Dawley rats: role of the renal innervation. Acta Physiol (Oxf). 2015;214:390–401.

    Article  CAS  Google Scholar 

  19. Hendel MD, Collister JP. Renal denervation attenuates long-term hypertensive effects of Angiotensin II in the rat. Clin Exp Pharmacol Physiol. 2006;33:1225–30.

    Article  CAS  PubMed  Google Scholar 

  20. Esler M. The sympathetic nervous system in hypertension: back to the future? Curr Hypertens Rep. 2015;17:11.

    Article  PubMed  CAS  Google Scholar 

  21. Luft FC, et al. Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins. Hypertension. 1989;14:396–403.

    Article  CAS  PubMed  Google Scholar 

  22. Foss JD, Fink GD, Osborn JW. Reversal of genetic salt-sensitive hypertension by targeted sympathetic ablation. Hypertension. 2013;61:806–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. King AJ, Osborn JW, Fink GD. Splanchnic circulation is a critical neural target in angiotensin II salt hypertension in rats. Hypertension. 2007;50:547–56.

    Article  CAS  PubMed  Google Scholar 

  24. Yoshimoto M, Miki K, Fink GD, King A, Osborn JW. Chronic angiotensin II infusion causes differential responses in regional sympathetic nerve activity in rats. Hypertension. 2010;55:644–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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. 2006;290:R701–8.

    Article  CAS  PubMed  Google Scholar 

  26. Yao Y, et al. The effect of losartan on differential reflex control of sympathetic nerve activity in chronic kidney disease. J Hypertens. 2015;33:1249–60.

    Article  CAS  PubMed  Google Scholar 

  27. Shi Z, Brooks VL. Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen. J Physiol. 2015;593:1633–47.

    Article  CAS  PubMed  Google Scholar 

  28. Bristow JD, et al. The influence of ventilation, carbon dioxide and hypoxia on the baroreceptor reflex in man. J Physiol. 1968;198:102; passim-103.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  30. Cowley Jr AW. Long-term control of arterial blood pressure. Physiol Rev. 1992;72:231–300.

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  32. Lohmeier TE, Iliescu R. The baroreflex as a long-term controller of arterial pressure. Physiology (Bethesda). 2015;30:148–58.

    CAS  Google Scholar 

  33. Iliescu R, Tudorancea I, Lohmeier TE. Baroreflex activation: from mechanisms to therapy for cardiovascular disease. Curr Hypertens Rep. 2014;16:453.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  35. Lohmeier TE. The sympathetic nervous system and long-term blood pressure regulation. Am J Hypertens. 2001;14:147S–54.

    Article  CAS  PubMed  Google Scholar 

  36. Kuroki MT, Guzman PA, Fink GD, Osborn JW. Time-dependent changes in autonomic control of splanchnic vascular resistance and heart rate in ANG II-salt hypertension. Am J Physiol Heart Circ Physiol. 2012;302:H763–9.

    Article  CAS  PubMed  Google Scholar 

  37. Rahman AA, Shahid IZ, Pilowsky PM. Differential cardiorespiratory and sympathetic reflex responses to microinjection of neuromedin U in rat rostral ventrolateral medulla. J Pharmacol Exp Ther. 2012;341:213–24.

    Article  CAS  PubMed  Google Scholar 

  38. Oparil S, Chen YF, Berecek K, Calhoun DA, Wyss JM. The role of the central nervous system in hypertension. In Laragh J.H.M., Brenner, B.M. (eds.), Hypertension: pathophysiology, diagnosis and management. 2nd ed. New York: Raven; 1995.

    Google Scholar 

  39. Esler M, et al. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension. 2006;48:787–96.

    Article  CAS  PubMed  Google Scholar 

  40. Dampney RA. Arcuate nucleus—a gateway for insulin’s action on sympathetic activity. J Physiol. 2011;589:2109–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 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. 2008;12:717–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Osborn JW, et al. Effect of subfornical organ lesion on the development of mineralocorticoid-salt hypertension. Brain Res. 2006;1109:74–82.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wyss JM, Yang RH, Oparil S. Lesions of the anterior hypothalamic area increase arterial pressure in NaCl-sensitive spontaneously hypertensive rats. J Auton Nerv Syst. 1990;31:21–9.

    Article  CAS  PubMed  Google Scholar 

  45. Shoemaker JK, Norton KN, Baker J, Luchyshyn T. Forebrain organization for autonomic cardiovascular control. Auton Neurosci. 2015;188:5–9.

    Article  PubMed  Google Scholar 

  46. de Morree HM, Szabo BM, Rutten GJ, Kop WJ. Central nervous system involvement in the autonomic responses to psychological distress. Neth Heart J. 2013;21:64–9.

    Article  PubMed  Google Scholar 

  47. Cechetto DF. Cortical control of the autonomic nervous system. Exp Physiol. 2014;99:326–31.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 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. 2002;282:H1592–602.

    Article  CAS  PubMed  Google Scholar 

  50. 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. 1994;7:536–42.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  52. 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. 1991;9:1127–33.

    CAS  PubMed  Google Scholar 

  53. Heesch CM, Crandall ME, Turbek JA. Converting enzyme inhibitors cause pressure-independent resetting of baroreflex control of sympathetic outflow. Am J Physiol. 1996;270:R728–37.

    CAS  PubMed  Google Scholar 

  54. Lantelme P, Cerutti C, Lo M, Paultre CZ, Ducher M. Mechanisms of spontaneous baroreflex impairment in lyon hypertensive rats. Am J Physiol. 1998;275:R920–5.

    CAS  PubMed  Google Scholar 

  55. Baltatu O, et al. Alterations in blood pressure and heart rate variability in transgenic rats with low brain angiotensinogen. Hypertension. 2001;37:408–13.

    Article  CAS  PubMed  Google Scholar 

  56. 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. 2007;9:242–7.

    Article  CAS  PubMed  Google Scholar 

  57. Biancardi VC, Son SJ, Ahmadi S, Filosa JA, Stern JE. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier. Hypertension. 2014;63:572–9.

    Article  CAS  PubMed  Google Scholar 

  58. 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. 2007;293:R2267–78.

    Article  CAS  PubMed  Google Scholar 

  59. Fink GD, Bruner CA, Mangiapane ML. Area postrema is critical for angiotensin-induced hypertension in rats. Hypertension. 1987;9:355–61.

    Article  CAS  PubMed  Google Scholar 

  60. Matsumura K, Averill DB, Ferrario CM. Role of AT1 receptors in area postrema on baroreceptor reflex in spontaneously hypertensive rats. Brain Res. 1999;850:166–72.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Davisson RL, et al. The brain renin-angiotensin system contributes to the hypertension in mice containing both the human renin and human angiotensinogen transgenes. Circ Res. 1998;83:1047–58.

    Article  CAS  PubMed  Google Scholar 

  63. Sinnayah P, et al. Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response. Circ Res. 2006;99:1125–31.

    Article  CAS  PubMed  Google Scholar 

  64. Doobay MF, et al. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. 2007;292:R373–81.

    Article  CAS  PubMed  Google Scholar 

  65. Sakai K, et al. Local production of angiotensin II in the subfornical organ causes elevated drinking. J Clin Invest. 2007;117:1088–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Young CN, et al. ER stress in the brain subfornical organ mediates angiotensin-dependent hypertension. J Clin Invest. 2012;122:3960–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Dai L, Smith PM, Kuksis M, Ferguson AV. Apelin acts in the subfornical organ to influence neuronal excitability and cardiovascular function. J Physiol. 2013;591:3421–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Young CN, Morgan DA, Butler SD, Mark AL, Davisson RL. The brain subfornical organ mediates leptin-induced increases in renal sympathetic activity but not its metabolic effects. Hypertension. 2013;61:737–44.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  73. 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. 1997;29:3365–74.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  75. Kimura 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. 2005;96:252–60.

    Article  CAS  PubMed  Google Scholar 

  76. Zhang F, et al. Decreased levels of cytochrome P450 2E1-derived eicosanoids sensitize renal arteries to constrictor agonists in spontaneously hypertensive rats. Hypertension. 2005;45:103–8.

    Article  CAS  PubMed  Google Scholar 

  77. Zalba G, et al. Vascular NADH/NADPH oxidase is involved in enhanced superoxide production in spontaneously hypertensive rats. Hypertension. 2000;35:1055–61.

    Article  CAS  PubMed  Google Scholar 

  78. 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). 2006;110:243–53.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  80. Hirooka Y, et al. Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats. Hypertens Res. 2006;29:49–56.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  83. Zimmerman MC, et al. Superoxide mediates the actions of angiotensin II in the central nervous system. Circ Res. 2002;91:1038–45.

    Article  CAS  PubMed  Google Scholar 

  84. 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. 2004;95:210–6.

    Article  CAS  PubMed  Google Scholar 

  85. Hoopes SL, Garcia V, Edin ML, Schwartzman ML, Zeldin DC. Vascular actions of 20-HETE. Prostaglandins Other Lipid Mediat. 2015;120:9–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. 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. 2007;72:683–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  88. 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. 2001;14:90S–7.

    Article  CAS  PubMed  Google Scholar 

  89. Muthalif MM, et al. Angiotensin II-induced hypertension: contribution of Ras GTPase/mitogen-activated protein kinase and cytochrome P450 metabolites. Hypertension. 2000;36:604–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  91. Hoagland KM, Maier KG, Roman RJ. Contributions of 20-HETE to the antihypertensive effects of Tempol in Dahl salt-sensitive rats. Hypertension. 2003;41:697–702.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  93. 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. 2004;43:623–8.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  96. 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. 2008;21:685–90.

    Article  CAS  PubMed  Google Scholar 

  97. Bubb KJ, et al. Activation of neuronal transient receptor potential vanilloid 1 channel underlies 20-hydroxyeicosatetraenoic acid-induced vasoactivity: role for protein kinase A. Hypertension. 2013;62:426–33.

    Article  CAS  PubMed  Google Scholar 

  98. Toth P, et al. Role of 20-HETE, TRPC channels, and BKCa in dysregulation of pressure-induced Ca2+ signaling and myogenic constriction of cerebral arteries in aged hypertensive mice. Am J Physiol Heart Circ Physiol. 2013;305:H1698–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Harder DR, et al. Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels. Am J Physiol. 1994;266:H2098–107.

    CAS  PubMed  Google Scholar 

  100. 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. 1994;266:H1879–85.

    CAS  PubMed  Google Scholar 

  101. Frisbee JC, Roman RJ, Murali Krishna U, Falck JR, Lombard JH. Altered mechanisms underlying hypoxic dilation of skeletal muscle resistance arteries of hypertensive versus normotensive Dahl rats. Microcirculation. 2001;8:115–27.

    Article  CAS  PubMed  Google Scholar 

  102. Gebremedhin D, et al. Production of 20-HETE and its role in autoregulation of cerebral blood flow. Circ Res. 2000;87:60–5.

    Article  CAS  PubMed  Google Scholar 

  103. Gordon GR, Mulligan SJ, MacVicar BA. Astrocyte control of the cerebrovasculature. Glia. 2007;55:1214–21.

    Article  PubMed  Google Scholar 

  104. Imig JD, Simpkins AN, Renic M, Harder DR. Cytochrome P450 eicosanoids and cerebral vascular function. Expert Rev Mol Med. 2011;13, e7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Tacconelli S, Patrignani P. Inside epoxyeicosatrienoic acids and cardiovascular disease. Front Pharmacol. 2014;5:239.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Metea MR, Newman EA. Signalling within the neurovascular unit in the mammalian retina. Exp Physiol. 2007;92:635–40.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Cambj-Sapunar L, Yu M, Harder DR, Roman RJ. Contribution of 5-hydroxytryptamine1B receptors and 20-hydroxyeiscosatetraenoic acid to fall in cerebral blood flow after subarachnoid hemorrhage. Stroke. 2003;34:1269–75.

    Article  PubMed  Google Scholar 

  108. Yousif MH, Benter IF, Roman RJ. Cytochrome P450 metabolites of arachidonic acid play a role in the enhanced cardiac dysfunction in diabetic rats following ischaemic reperfusion injury. Auton Autacoid Pharmacol. 2009;29:33–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Renic M, et al. Effect of 20-HETE inhibition on infarct volume and cerebral blood flow after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab. 2009;29:629–39.

    Article  CAS  PubMed  Google Scholar 

  110. Toth P, et al. Treatment with the cytochrome P450 omega-hydroxylase inhibitor HET0016 attenuates cerebrovascular inflammation, oxidative stress and improves vasomotor function in spontaneously hypertensive rats. Br J Pharmacol. 2013;168:1878–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Dunn KM, et al. 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. 2008;295:H2455–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Ward NC, et al. Cytochrome P450 metabolites of arachidonic acid are elevated in stroke patients compared with healthy controls. Clin Sci (Lond). 2011;121:501–7.

    Article  CAS  Google Scholar 

  113. Deng S, et al. CYP4F2 gene V433M polymorphism is associated with ischemic stroke in the male Northern Chinese Han population. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:664–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Scott H. Carlson Ph.D.

  2. Departments of Cellular and Molecular Physiology and Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA

    Sean Stocker Ph.D.

  3. Departments of Cell Developmental and Integrative Biology and Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    J. Michael Wyss Ph.D.

Authors
  1. Scott H. Carlson Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sean Stocker Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Michael Wyss Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Michael Wyss Ph.D. .

Editor information

Editors and Affiliations

  1. Departments of Neurological Surgery and Neurology and Neurotherapeutics , University of Texas Southwestern Medical Center , Dallas, Texas, USA

    Venkatesh Aiyagari

  2. Michigan State University Department of Translational Science & Molecular Medicine, Mercy Health Hauenstein Neurosciences, Grand Rapids, Michigan, USA

    Philip B. Gorelick

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Carlson, S.H., Stocker, S., Wyss, J.M. (2016). Mechanisms Underlying Essential Hypertension: Neurogenic and Non-neurogenic Contributors. In: Aiyagari, V., Gorelick, P. (eds) Hypertension and Stroke. Clinical Hypertension and Vascular Diseases. Humana Press, Cham. https://doi.org/10.1007/978-3-319-29152-9_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-29152-9_4

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-29150-5

  • Online ISBN: 978-3-319-29152-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation