Role of K+ channels in A2A adenosine receptor-mediated dilation of the pressurized renal arcuate artery

1 Adenosine A(2A) receptor-mediated renal vasodilation was investigated by measuring the lumenal diameter of pressurized renal arcuate arteries isolated from the rabbit. 2 The selective A(2A) receptor agonist CGS21680 dilated the arteries with an EC50 of 130 nM. The CGS21680-induced vasodilation was, on average, 34% less in endothelium-denuded arteries. 3 The maximum response and the EC50, for CGS21680-induced vasodilation in endothelium-intact arteries were not significantly affected by incubation with the K+ channel blockers apamin (100 nM, iberiotoxin (100 nM), 3,4-diaminopyridine (1 mM), glibenclamide (1 mu M) or Ba2+ (10 mu M). However, a cocktail mixture of these blockers did significantly inhibit the maximum response by almost 40%, and 1 mM Ba2+ alone or 1 mM Ba2+ in addition to the cocktail inhibited the maximum CGS21680-response by 58% and about 75% respectively. 4 CCS21680-induced vasodilation was strongly inhibited when the extracellular K+ level was raised to 20 mM even though the dilator response to 1 mu M levcromakalim, a K-ATP channel opener drug, was unaffected. 5 CGS21680-induced vasodilation was inhibited by 10 mu M ouabain, an inhibitor of Na+/K+-ATPase, but ouabain had a similar inhibitory effect on vasodilation induced by 30 nM nicardipine (a dihydropyridine Ca2+ antagonist) or 1 mu M levcromakalim. 6 The data suggest that K+ channel activation does play a role in A(2A) receptor-mediated renal vasodilation. The inhibitory effect of raised extracellular K+ levels on the A(2A) response may be due to K+-induced stimulation of Na+/K+-ATPase.