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 mumol.l-1 3H-noradrenaline was evoked by electrical stimulation (1 Hz, during 5 min) or potassium (25-100 mmol.l-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) x 10(-5).pulse-1, n = 10; P < 0.05]. Neither NG-nitro-L-arginine methyl ester (L-NAME) (up to 300 mumol.l-1) nor indomethacin (up to 30 mumol.l-1), nor endothelin-1 (up to 30 nmol.l-1), nor suramin (up to 300 mumol.l-1) changed tritium release evoked 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.
Vaz-da-Silva
M J
MJ
Institute of Pharmacology and Therapeutics, Porto, Portugal.
Guimarães
S
S
Moura
D
D
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007553:Isotope Labeling; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D013498:Suramin / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014316:Tritium; D014970:Xanthines / Q000494:pharmacology
D019332:Endothelin-1; D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D013757:Tetraethylammonium Compounds; D014970:Xanthines; D014316:Tritium; C048599:N(6)-cyclopentyladenosine; D013498:Suramin; D019789:Tetraethylammonium; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019001:Nitric Oxide Synthase; D000241:Adenosine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine