Current Hypertension Reports

, Volume 9, Issue 3, pp 222–227 | Cite as

Cardiovascular effects of angiotensin II in the rostral ventrolateral medulla: The push-pull hypothesis

  • R. A. L. DampneyEmail author
  • P. S. P. Tan
  • M. J. Sheriff
  • M. A. P. Fontes
  • J. Horiuchi


Neurons within the rostral ventrolateral medulla (RVLM) play a pivotal role in the tonic and phasic control of blood pressure. This region also contains a high density of angiotensin II type 1 (AT1) receptors. There is evidence that tonic activation of AT1 receptors in the RVLM contributes to an increased sympathetic vasomotor activity in some models of hypertension. At the same time, under certain conditions, activation of AT1 receptors in the RVLM can cause sympathoinhibition. In this review we argue that the effect of endogenous angiotensin II in the RVLM on sympathetic vasomotor activity depends upon the balance between tonic excitatory and inhibitory effects on sympathetic premotor neurons mediated by AT1 receptors within this region, and that this balance may be altered in different physiological or pathophysiological conditions.


Ventrolateral Medulla Rostral Ventrolateral Medulla AT1a Receptor RVLM Neuron Endogenous Angiotensin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Allen AM, Moeller I, Jenkins TA, et al.: Angiotensin receptors in the nervous system. Brain Res Bull 1998, 47:17–28.PubMedCrossRefGoogle Scholar
  2. 2.
    McKinley MJ, Albiston AL, Allen AM, et al.: The brain renin-angiotensin system: location and physiological roles. Int J Biochem Cell Biol 2003, 35:901–918.PubMedCrossRefGoogle Scholar
  3. 3.
    Mendelsohn FAO, Quirion R, Saavedra JM, et al.: Autoradiographic localization of angiotensin II receptors in rat brain. Proc Nat Acad Sci U S A 1984, 81:1575–1579.CrossRefGoogle Scholar
  4. 4.
    Mendelsohn FAO, Allen AM, Clevers J, et al.: Localization of angiotensin II receptor binding in rabbit brain by in vitro autoradiography. J Comp Neurol 1988, 270:372–384.PubMedCrossRefGoogle Scholar
  5. 5.
    Gao L, Wang W, Li YL, et al.: Sympathoexcitation by central Ang II: roles for AT1 receptor upregulation and NAD(P)H oxidase in RVLM. Am J Physiol 2005, 288:H2271–H2279.Google Scholar
  6. 6.
    Gao L, Wang W, Li YL, et al.: Superoxide mediates sympathoexcitation in heart failure: roles of angiotensin II and NAD(P)H oxidase. Circ Res 2004, 95:937–944.PubMedCrossRefGoogle Scholar
  7. 7.
    Morimoto S, Cassell MD, Sigmund CD: Glia-and neuronspecific expression of the renin-angiotensin system in brain alters blood pressure, water intake, and salt preference. J Biol Chem 2002, 277:33235–33241.PubMedCrossRefGoogle Scholar
  8. 8.
    Huang BS, Leenen FH: Both brain angiotensin II and “ouabain” contribute to sympathoexcitation and hypertension in Dahl S rats on high salt intake. Hypertension 1998, 32:1028–1033.PubMedGoogle Scholar
  9. 9.
    Ye S, Zhong H, Duong VN, Campese VM: Losartan reduces central and peripheral sympathetic nerve activity in a rat model of neurogenic hypertension. Hypertension 2002, 39:1101–1106.PubMedCrossRefGoogle Scholar
  10. 10.
    Tan PSP, Potas JR, Killinger S, et al.: Angiotensin II evokes hypotension and renal sympathoinhibition from a highly restricted region in the nucleus tractus solitarii. Brain Res 2005, 1036:70–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Kasparov S, Paton JFR: Differential effects of angiotensin II in the nucleus tractus solitarii of the rat: plausible neuronal mechanism. J Physiol 1999, 521:227–238.PubMedCrossRefGoogle Scholar
  12. 12.
    Dampney RAL, Horiuchi J, Tagawa T, et al.: Medullary and supramedullary mechanisms regulating sympathetic vasomotor tone. Acta Physiol Scand 2003, 177:209–218.PubMedCrossRefGoogle Scholar
  13. 13.
    Dampney RAL: The subretrofacial vasomotor nucleus: anatomical, chemical and pharmacological properties and role in cardiovascular regulation. Prog Neurobiol 1994, 42:197–227.PubMedCrossRefGoogle Scholar
  14. 14.
    Guyenet PG: The sympathetic control of blood pressure. Nature Rev Neurosci 2006, 7:335–346.CrossRefGoogle Scholar
  15. 15.
    Menezes RCA, Fontes MAP: Cardiovascular effects produced by activation of GABA receptors in the rostral ventrolateral medulla of conscious rats. Neuroscience 2007, 144:336–343.PubMedCrossRefGoogle Scholar
  16. 16.
    Sved AF, Ito S, Sved JC: Brainstem mechanisms of hypertension: role of the rostral ventrolateral medulla. Curr Hypert Rep 2003, 5:262–268.Google Scholar
  17. 17.
    Sun MK, Young BS, Hackett JT, Guyenet PG: Reticulospinal pacemaker neurons of the rat rostral ventrolateral medulla with putative sympathoexcitatory function: an intracellular study in vitro. Brain Res 1988, 442:229–239.PubMedCrossRefGoogle Scholar
  18. 18.
    Hu L, Zhu DN, Yu Z, et al.: Expression of angiotensin II type 1 (AT1) receptor in the rostral ventrolateral medulla in rats. J Appl Physiol 2002, 92:2153–2161.PubMedCrossRefGoogle Scholar
  19. 19.
    Li YW, Guyenet PG: Angiotensin II decreases a resting K+ conductance in rat bulbospinal neurons of the C1 area. Circ Res 1996, 78:274–282.PubMedGoogle Scholar
  20. 20.
    Barnes KL, DeWeese DM, Andresen MC: Angiotensin potentiates excitatory sensory synaptic transmission to medial solitary tract nucleus neurons. Am J Physiol 2003, 284:R1340–R1353.Google Scholar
  21. 21.
    Huang J, Hara Y, Anrather J, et al.: Angiotensin II subtype 1A (AT1A) receptors in the rat sensory vagal complex: subcellular localization and association with endogenous angiotensin. Neuroscience 2003, 122:21–36.PubMedCrossRefGoogle Scholar
  22. 22.
    Allen AM, Dampney RAL, Mendelsohn FAO: Angiotensin receptor binding and pressor effects in cat subretrofacial nucleus. Am J Physiol 1988, 255:H1011–H1017.PubMedGoogle Scholar
  23. 23.
    Averill DB, Tsuchihashi T, Khosla MC, Ferrario CM: Losartan, nonpeptide angiotensin II-type 1 (AT1) receptor antagonist, attenuates pressor and sympathoexcitatory responses evoked by angiotensin II and L-glutamate in rostral ventrolateral medulla. Brain Res 1994, 665:245–252.PubMedCrossRefGoogle Scholar
  24. 24.
    Hirooka Y, Potts PD, Dampney RAL: Role of angiotensin II receptor subtypes in mediating the sympathoexcitatory effects of exogenous and endogenous angiotensin peptides in the rostral ventrolateral medulla of the rabbit. Brain Res 1997, 772:107–114.PubMedCrossRefGoogle Scholar
  25. 25.
    Hirooka Y, Head GA, Potts PD, et al.: Medullary neurons activated by angiotensin II in the conscious rabbit. Hypertension 1996, 27:287–296.PubMedGoogle Scholar
  26. 26.
    Matsuura T, Kumagai H, Onimaru H, et al.: Electrophysiological properties of rostral ventrolateral medulla neurons in angiotensin II 1a receptor knockout mice. Hypertension 2005, 46:349–354.PubMedCrossRefGoogle Scholar
  27. 27.
    Allen AM, Dosanjh JK, Erac M, et al.: Expression of constitutively active angiotensin receptors in the rostral ventrolateral medulla increases blood pressure. Hypertension 2006, 47:1054–1061.PubMedCrossRefGoogle Scholar
  28. 28.
    Ito S, Hiratsuka M, Komatsu K, et al.: Ventrolateral medulla AT1 receptors support arterial pressure in Dahl salt-sensitive rats. Hypertension 2003, 41:744–750.PubMedCrossRefGoogle Scholar
  29. 29.
    Ito S, Komatsu K, Tsukamoto K, et al.: Ventrolateral medulla AT1 receptors support blood pressure in hypertensive rats. Hypertension 2002, 40:552–559.PubMedCrossRefGoogle Scholar
  30. 30.
    Tagawa T, Dampney RAL: AT(1) receptors mediate excitatory inputs to rostral ventrolateral medulla pressor neurons from hypothalamus. Hypertension 1999, 34:1301–1307.PubMedGoogle Scholar
  31. 31.
    Allen AM: Blockade of angiotensin AT1-receptors in the rostral ventrolateral medulla of spontaneously hypertensive rats reduces blood pressure and sympathetic nerve discharge. J Renin-Angiotensin-Aldosterone Syst 2001, 2(Suppl 1):S120–S124.Google Scholar
  32. 32.
    Fontes MAP, Baltatu O, Caligiorne SM, et al.: Angiotensin peptides acting at rostral ventrolateral medulla contribute to hypertension of TGR(mREN2)27 rats. Physiol Genomics 2000, 2:137–142.PubMedGoogle Scholar
  33. 33.
    Mayorov DN, Head GA: AT1 receptors in the RVLM mediate pressor responses to emotional stress in rabbits. Hypertension 2003, 41:1168–1173.PubMedCrossRefGoogle Scholar
  34. 34.
    Tagawa T, Fontes MAP, Potts PD, et al.: The physiological role of AT1 receptors in the ventrolateral medulla. Braz J Med Biol Res 2000, 33:643–652.PubMedCrossRefGoogle Scholar
  35. 35.
    Fontes MAP, Martins Pinge MC, Naves V, et al.: Cardiovascular effects produced by microinjection of angiotensins and angiotensin antagonists into the ventrolateral medulla of freely moving rats. Brain Res 1997, 750:305–310.PubMedCrossRefGoogle Scholar
  36. 36.
    Baltatu O, Fontes MAP, Campagnole-Santos MJ, et al.: Alterations of the renin-angiotensin system at the RVLM of transgenic rats with low brain angiotensinogen. Am J Physiol 2001, 280:R428–R433.Google Scholar
  37. 37.
    Bertram D, Coote JH: Inhibitory effect of angiotensin II on barosensitive rostral ventrolateral medulla neurons of the rat. Clin Exp Pharmacol Physiol 2001, 28:1112–1114.PubMedCrossRefGoogle Scholar
  38. 38.
    Sheriff MJ, Fontes MAP, Killinger S, et al.: Blockade of AT1 receptors in the rostral ventrolateral medulla increases sympathetic activity under hypoxic conditions. Am J Physiol 2006, 290:R733–R740.Google Scholar
  39. 39.
    Paton JFR, Boscan P, Murphy D, Kasparov S: Unravelling mechanisms of action of angiotensin II on cardiorespiratory function using in vivo gene transfer. Acta Physiol Scand 2001, 173:127–137.PubMedCrossRefGoogle Scholar
  40. 40.
    Kishi T, Hirooka Y, Sakai K, et al.: Overexpression of eNOS in the RVLM causes hypotension and bradycardia via GABA release. Hypertension 2001, 38:896–901.PubMedGoogle Scholar
  41. 41.
    Lind RW, Swanson LW, Ganten D: Organization of angiotensin II-immunoreactive cells and fibers in the rat central nervous system: an immunohistochemical study. Neuroendocrinology 1985, 40:2–24.PubMedGoogle Scholar
  42. 42.
    Lavoie JL, Cassell MD, Gross KW, Sigmund CD: Adjacent expression of renin and angiotensinogen in the rostral ventrolateral medulla using a dual-reporter transgenic model. Hypertension 2004, 43:1116–1119.PubMedCrossRefGoogle Scholar
  43. 43.
    Reja V, Goodchild AK, Phillips JK, Pilowsky PM: Upregulation of angiotensin AT1 receptor and intracellular kinase gene expression in hypertensive rats. Clin Exp Pharmacol Physiol 2006, 33:690–695.PubMedCrossRefGoogle Scholar
  44. 44.
    Veerasingham SJ, Raizada MK: Brain renin-angiotensin system dysfunction in hypertension: recent advances and perspectives. Br J Pharmacol 2003, 139:191–202.PubMedCrossRefGoogle Scholar
  45. 45.
    Seyedabadi M, Goodchild AK, Pilowsky PM: Differential role of kinases in brainstem of hypertensive and normotensive rats. Hypertension 2001, 38:1087–1092.PubMedGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  • R. A. L. Dampney
    • 1
    Email author
  • P. S. P. Tan
  • M. J. Sheriff
  • M. A. P. Fontes
  • J. Horiuchi
  1. 1.Department of Physiology, School of Medical Sciences and Bosch InstituteThe University of Sydney F13SydneyAustralia

Personalised recommendations