Intra-carotid angiotensin II activates tyrosine hydroxylase-expressing rostral ventrolateral medulla neurons following blood-brain barrier disruption in rats

Neuroscience. 2013 Aug 15;245:148-56. doi: 10.1016/j.neuroscience.2013.04.023. Epub 2013 Apr 19.

Abstract

Angiotensin II (Ang II) in the periphery and within the brain plays important roles in blood pressure control. Circulating angiotensin is normally excluded from the brain by the blood-brain barrier (BBB), but there is evidence that in some diseases there is disruption of the BBB that could allow circulating Ang II to access nuclei from which it is normally excluded, such as the rostral ventrolateral medulla (RVLM). We therefore investigated whether disruption of the BBB leads to increased activation by circulating Ang II of tyrosine hydroxylase (TH)-containing neurons in the RVLM. In anaesthetised rats, in which the BBB was disrupted with intracarotid hypertonic mannitol (1.6M, 2mL/kg), subsequent intracarotid infusion of a subpressor dose of Ang II (5ng/kg) activated ∼24% of TH-containing RVLM neurons whereas saline only activated ∼8% of TH neurons. Intracarotid pretreatment with the Ang II receptor type 1 (AT1R) blocker, losartan (20μg/kg), significantly reduced the number of TH cells activated to ∼11% (P<0.05, one-way analysis of variance, n=5). In summary, disruption of the BBB resulted in increased activation by circulating Ang II of TH-containing cells in the RVLM. The activation was reduced by losartan indicating a specific action on AT1Rs. These results suggest that disruption of the BBB allows entry of circulating Ang II into the RVLM, which could increase sympathetic outflow. This potential source of Ang II within the RVLM might be an important consideration when assessing sympathetic nerve activity in disease states associated with a compromised BBB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / blood*
  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism*
  • Carotid Arteries / drug effects
  • Carotid Arteries / metabolism*
  • Infusions, Intra-Arterial
  • Male
  • Mannitol / administration & dosage
  • Mannitol / toxicity
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Tyrosine 3-Monooxygenase / biosynthesis*

Substances

  • Angiotensin II
  • Mannitol
  • Tyrosine 3-Monooxygenase