Analysis of adenosine vascular effect in isolated rat aorta: possible role of Na+/K+-ATPase.
The present experiments were undertaken in order to examine the effect of adenosine in isolated rat aorta, to investigate the possible role of intact endothelium and endothelial relaxing factors in this action and to determine which population of adenosine receptors is involved in rat aorta response to adenosine. Adenosine (0.1-300 microM) produced concentration-dependent (intact rings: pD2=4.39+/-0.09) and endothelium-independent (denuded rings: pD2=4.52+/-0.12) relaxation of isolated rat aorta. In the presence of high concentration of K+ (100 mM) adenosine-evoked relaxation was significantly reduced (maximal relaxation in denuded rings: control - 92.1+/-9.8 versus K+- 54.4+/-5.0). Similar results were obtained after incubation of ouabain (100 microM) or glibenclamide (1 microM). In K+-free solution, K+ (1-10 mM)-induced rat aorta relaxant response was significantly inhibited by ouabain (100 microM). Application of indomethacin (10 microM), NG-nitro-L-arginine (10 microM) or tetraethylammonium (500 microM) did not alter the adenosine-elicited effect in rat aorta. 8-(3-Chlorostyril)-caffeine (0.3-3 microM), a selective A2A-receptor antagonist, significantly reduced adenosine-induced relaxation of rat aorta in a concentration-dependent manner (pKB=6.57). Conversely, 1,3-dipropyl-8-cyclopentylxanthine (10 nM), an A1-receptor antagonist, did not affect adenosine-evoked dilatation. These results indicate that in isolated rat aorta, adenosine produces endothelium-independent relaxation, which is most probably dependent upon activation of smooth muscle Na+/K+-ATPase, and opening of ATP-sensitive K+ channels, to a smaller extent. According to receptor analysis, vasorelaxant action of adenosine in rat aorta is partly induced by activation of smooth muscle adenosine A2A receptors.
Grbović
Leposava
L
Department of Clinical Pharmacology, Pharmacology and Toxicology, Medical Faculty, University of Belgrade, P.O. Box 840, 11000 Belgrade, Yugoslavia. miroslavr@beotel.yu
Radenković
Miroslav
M
D000241:Adenosine / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D000254:Sodium-Potassium-Exchanging ATPase; D000241:Adenosine