title: Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.
abstract: Nitric oxide (NO) seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS) inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS) was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells) and Confocal Microscopy. Results indicated that: 1) in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2) in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3) confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.
authors.affiliation: Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; LAQV/REQUIMTE, University of Porto, Porto, Portugal.
authors.forename: Joana Beatriz
authors.initials: JB
authors.lastname: Sousa
authors.affiliation: Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; LAQV/REQUIMTE, University of Porto, Porto, Portugal.
authors.forename: Maria Sofia
authors.initials: MS
authors.lastname: Vieira-Rocha
authors.affiliation: Department of Physiology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Arribas
authors.affiliation: Department of Physiology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: González
authors.affiliation: Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Fresco
authors.affiliation: Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; LAQV/REQUIMTE, University of Porto, Porto, Portugal.
authors.forename: Carmen
authors.initials: C
authors.lastname: Diniz
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D006439:Hemodynamics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D012039:Regional Blood Flow; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D000248:Adenosine Kinase