Lack of Endogenous Adenosine Tonus on Sympathetic Neurotransmission in Spontaneously Hypertensive Rat Mesenteric Artery

Abstract

BackgroundIncreased 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 ResultsThe 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.ConclusionData 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.

Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries

“…In mesenteric arteries, we have demonstrated previously that exocytosis (induced by electrical field stimulation) did not modify the amount of adenosine available at the extracellular space [25]. Therefore, adenosine accumulation in the present conditions could result from the transport of adenosine via nucleoside transporters or from adenosine kinase inhibition (adenosine kinase is inhibited by adenosine itself).…”

Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats

“…In these conditions, the contractile response to EFS was reduced only in segments from the O‐DR group, indicating that ATP contributes to this response. In line with these results, EFS‐induced ATP release was higher in mesenteric segments from O‐DR than O‐CR rats, as previously described (Rummery et al ., ; Sousa et al ., ), suggesting an increased contribution of ATP in neurovascular transmission in hypertension. Altogether, these observations indicate that the increased participation of sympathetic neurons observed in mesenteric segments from O‐DR animals is due to an increase in NA and ATP release from nerve terminals.…”

Vascular Sympathetic Neurotransmission and Endothelial Dysfunction

“…Another factor related with the relevance of vascular adenosine-mediated effects relies on adenosine receptor subtype distribution in the vasculature. All adenosine receptor subtypes have been identified not only in arteries, such as pulmonary [72], mesenteric [73][74][75][76][77], ear [73], aorta [78] and tail [51,52,[79][80][81], but also in veins [75,82]. In renal vessels, a role of adenosine receptors in sympathetic regulation was also demonstrated [83], conditioning the blood efflux Tissue preparations of mesenteric and tail arteries from WKY and SHR animals were superfused with Krebs-Henseleit.…”

“…In hypertensive arteries and veins, an impairment of the neuromodulation exerted by adenosine A 1 receptors [75][76][77]82] was described, contrasting with a preserved adenosine A 2A receptor-mediated facilitation of noradrenaline release [75][76][77]. Note that a redistribution of adenosine A 1 receptors from sympathetic nerves to Schwann cells was reported in hypertensive state while adenosine A 2A receptors, in sympathetic nerves, were preserved [77]. Particular relevant information relies on the location of adenosine receptors on the vascular wall layers contributing to the understanding of the functional role ascribed to adenosine receptors.…”