title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: REQUIMTE/FARMA, Departamento de Ciências do Medicamento, Laboratório de Farmacologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; MedInUP- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal.
authors.forename: Joana Beatriz
authors.initials: JB
authors.lastname: Sousa
authors.affiliation: REQUIMTE/FARMA, Departamento de Ciências do Medicamento, Laboratório de Farmacologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; MedInUP- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal.
authors.forename: Maria Sofia
authors.initials: MS
authors.lastname: Vieira-Rocha
authors.affiliation: Centro de Materiais, Universidade do Porto, Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sá
authors.affiliation: MedInUP- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal; Laboratório de Farmacologia e Neurobiologia/UMIB, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Ferreirinha
authors.affiliation: MedInUP- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal; Laboratório de Farmacologia e Neurobiologia/UMIB, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Correia-de-Sá
authors.affiliation: REQUIMTE/FARMA, Departamento de Ciências do Medicamento, Laboratório de Farmacologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; MedInUP- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Fresco
authors.affiliation: REQUIMTE/FARMA, Departamento de Ciências do Medicamento, Laboratório de Farmacologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; MedInUP- Centro de Investigação Farmacológica e Inovação Medicamentosa, Universidade do Porto, Porto, Portugal.
authors.forename: Carmen
authors.initials: C
authors.lastname: Diniz
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation* / Q000378:metabolism / Q000503:physiopathology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission
chemical_list: D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D000255:Adenosine Triphosphate; D000241:Adenosine; D009638:Norepinephrine