Adenosine and the endothelium-dependent modulation of 3H-noradrenaline release in the canine pulmonary artery

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 mol.1^{–1 3}H-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 N^G-nitro-l-arginine methyl ester (l-NAME) (up to 300 mol.l^–1) nor indomethacin (up to 30 ml.l^–1), nor endothelin-1 (up to 30 nmol.l^–1), nor suramin (up to 300 mol.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.