Abstract
This study aimed at characterizing the influence of endothelium on noradrenaline release from the canine pulmonary artery. Tritium overflow from intact or endothelium-free vessels preloaded with 0.2 μmol.1−1 3H-noradrenaline was evoked by electrical stimulation (1 Hz, during 5 min) or potassium (25–100 mmol. 1−1).
The fractional release of tritium evoked by electrical stimulation was increased by removing the endothelium [from 1.7 (1.2; 2.4) to 2.7(2.3; 3.2) × 10−5. pulse−1, n = 10; P < 0.05]. Neither NG-nitro-l-arginine methyl ester (l-NAME) (up to 300 μmol.l−1) nor indomethacin (up to 30 μml.l−1), nor endothelin-1 (up to 30 nmol.l−1), nor suramin (up to 300 μmol.l−1) changed tritium release evolved by electrical stimulation. In contrast, the selective A1-adenosine antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (3.3-33 nmol.l−1) concentration-dependently increased, and the selective A1-adenosine agonist N6-cyclopentyladenosine (CPA) (3.3–100 nmol. l−1) concentration-dependently decreased the evoked release of noradrenaline. Since the effects of DPCPX were observed in endothelium-intact tissues only, it may be concluded that adenosine secreted by the endothelium activates prejunctional release-inhibiting A1-receptors. Tetraethylammonium (TEA) (3.3–33 mmol. l−1) enhanced tritium overflow evoked by electrical stimulation more in endothelium-free than in endothelium-intact vessels, indicating that some K+-channel opener is involved in the inhibitory role of endothelium on noradrenaline release. Since it had been previously shown that A1-adenosine receptors are coupled to K+-channels, it is suggested that adenosine may inhibit noradrenaline release through the opening of K+-channels.
In conclusion, the results show that in the canine pulmonary artery, adenosine is a good candidate for the endothelium-dependent inhibitory factor which is responsible for the reduction of noradrenaline release evoked by electrical stimulation.
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Vaz-da-Silva, M., Guimarães, S. & Moura, D. Adenosine and the endothelium-dependent modulation of 3H-noradrenaline release in the canine pulmonary artery. Naunyn-Schmiedeberg's Arch Pharmacol 352, 640–645 (1995). https://doi.org/10.1007/BF00171323
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DOI: https://doi.org/10.1007/BF00171323