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

Abstract

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 [ 3 H]-noradrenaline release experiments. Purine content was determined by HPLC with fluorescence detection. Localization of adenosine A 1 or A 2A 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 A 1 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 A 2A receptor-mediated effects were absent in arteries from both strains. Immunohistochemistry revealed an adenosine A 1 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 A 1 receptors in hypertensive arteries may explain the latter effect. © 2014 Sousa et al.