Isolated rat inferior mesenteric artery response to adenosine: possible participation of Na+/K+-ATPase and potassium channels.
Adenosine (10(-7)-3 x 10(-4) M) produced concentration-dependent and endothelium-independent relaxation of isolated rat inferior mesenteric artery. Application of indomethacin (10(-5) M) or N(G)-nitro-L-arginine (10(-5) M) did did not alter adenosine-elicited relaxation. Conversely, in the presence of high concentration of K+ (100 mM), ouabain (10(-4)) or combination of tetraethylammonium (5 x 10(-4) M) and glibenclamide (10(-6) M), adenosine-evoked relaxant effect was significantly reduced. In K+-free solution, 1-3 mM potassium induced relaxation, which was partially reversed by ouabain (10(-4) M). 1,3-Dipropyl-8-cyclopentylxanthine (10(-9) M), an A1-receptor antagonist, did not affect adenosine-evoked relaxation. Oppositely, 8-(3-chlorostyryl)-caffeine (3 x 10(-7)-10(-6) M), a selective A2A receptor antagonist, significantly inhibited adenosine-induced relaxation in a concentration-dependent manner (pA2 = 6.74). These results indicate that in the isolated rat inferior mesenteric artery, adenosine produces endothelium-independent relaxation, which is partly induced by activation of smooth muscle adenosine A2A receptors, and further mediated by the activation of smooth muscle Na+/K+-ATPase and opening of mixed population of K+ channels.
Radenković
Miroslav
M
Department of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, Dr Subotića 1, P.O. Box 840, 11000 Belgrade, Serbia and Montenegro. miroslavr@beotel.net
Grbović
Leposava
L
Pesić
Srdan
S
Stojić
Dragica
D
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D017537:Mesenteric Artery, Inferior / Q000187:drug effects* / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D043705:Receptor, Adenosine A2A; D014665:Vasodilator Agents; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; D010042:Ouabain; D019789:Tetraethylammonium; D000254:Sodium-Potassium-Exchanging ATPase; D000241:Adenosine; D011188:Potassium; D005905:Glyburide