Compromised blood-brain barrier permeability: novel mechanism by which circulating angiotensin II signals to sympathoexcitatory centres during hypertension

J Physiol. 2016 Mar 15;594(6):1591-600. doi: 10.1113/JP271584. Epub 2015 Dec 21.


Angiotensin II (AngII) is a pivotal peptide implicated in the regulation of blood pressure. In addition to its systemic vascular and renal effects, AngII acts centrally to modulate the activities of neuroendocrine and sympathetic neuronal networks, influencing in turn sympatho-humoral outflows to the circulation. Moreover, a large body of evidence supports AngII signalling dysregulation as a key mechanism contributing to exacerbated sympathoexcitation during hypertension. Due to its hydrophilic actions, circulating AngII does not cross the blood-brain barrier (BBB), signalling to the brain via the circumventricular organs which lack a tight BBB. In this review, we present and discuss recent studies from our laboratory showing that elevated circulating levels of AngII during hypertension result in disruption of the BBB integrity, allowing access of circulating AngII to critical sympathoexcitatory brain centres such as the paraventricular nucleus of the hypothalamus and the rostral ventrolateral medulla. We propose the novel hypothesis that AngII-driven BBB breakdown constitutes a complementary mechanism by which circulating AngII, working in tandem with the central renin-angiotensin system, further exacerbates sympatho-humoral activation during hypertension. These results are discussed within the context of a growing body of evidence in the literature supporting AngII as a pro-inflammatory signal, and brain microglia as key cell targets mediating central AngII actions during hypertension.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin II / blood*
  • Animals
  • Blood-Brain Barrier / metabolism*
  • Capillary Permeability*
  • Humans
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Sympathetic Nervous System / physiology*
  • Sympathetic Nervous System / physiopathology


  • Angiotensin II