Lack of endogenous adenosine tonus on sympathetic neurotransmission in spontaneously hypertensive rat mesenteric artery

PLoS One. 2014 Aug 26;9(8):e105540. doi: 10.1371/journal.pone.0105540. eCollection 2014.


Background: Increased sympathetic activity has been implicated in hypertension. Adenosine has been shown to play a role in blood flow regulation. In the present study, the endogenous adenosine neuromodulatory role, in mesenteric arteries from normotensive and spontaneously hypertensive rats, was investigated.

Methods and results: The role of endogenous adenosine in sympathetic neurotransmission was studied using electrically-evoked [3H]-noradrenaline release experiments. Purine content was determined by HPLC with fluorescence detection. Localization of adenosine A1 or A2A receptors in adventitia of mesenteric arteries was investigated by Laser Scanning Confocal Microscopy. Results indicate a higher electrically-evoked noradrenaline release from hypertensive mesenteric arteries. The tonic inhibitory modulation of noradrenaline release is mediated by adenosine A1 receptors and is lacking in arteries from hypertensive animals, despite their purine levels being higher comparatively to those determined in normotensive ones. Tonic facilitatory adenosine A2A receptor-mediated effects were absent in arteries from both strains. Immunohistochemistry revealed an adenosine A1 receptors redistribution from sympathetic fibers to Schwann cells, in adventitia of hypertensive mesenteric arteries which can explain, at least in part, the absence of effects observed for these receptors.

Conclusion: Data highlight the role of purines in hypertension revealing that an increase in sympathetic activity in hypertensive arteries is occurring due to a higher noradrenaline/ATP release from sympathetic nerves and the loss of endogenous adenosine inhibitory tonus. The observed nerve-to-glial redistribution of inhibitory adenosine A1 receptors in hypertensive arteries may explain the latter effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Male
  • Mesenteric Arteries / innervation*
  • Mesenteric Arteries / metabolism
  • Mesenteric Arteries / physiopathology*
  • Norepinephrine / metabolism
  • Rats
  • Rats, Inbred SHR
  • Receptor, Adenosine A1 / metabolism
  • Receptor, Adenosine A2A / metabolism
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology
  • Synaptic Transmission*


  • Receptor, Adenosine A1
  • Receptor, Adenosine A2A
  • Adenosine Triphosphate
  • Adenosine
  • Norepinephrine

Grant support

This work was funded by FEDER through the Program of Operational Competitiveness Factors–COMPETE and National Funds and by Strategic Projects framework for Scientific Research Units of R&D (REEQ/1168/SAU/2005, REEQ/1264/SAU/2005, PEst-OE/SAU/UI0215/2011 and PEst-OE/SAU/UI0215/2014) through FCT – Foundation for Science and Technology. JBS thanks FCT for her PhD grant (SFRH/BD//2009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.