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

1. Adenosine A2A receptor-mediated renal vasodilation was investigated by measuring the lumenal diameter of pressurized renal arcuate arteries isolated from the rabbit. 2. The selective A2A 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 microM) or Ba2+ (10 microM). 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. CGS21680-induced vasodilation was strongly inhibited when the extracellular K+ level was raised to 20 mM even though the dilator response to 1 microM levcromakalim, a K(ATP) channel opener drug, was unaffected. 5. CGS21680-induced vasodilation was inhibited by 10 microM 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 microM 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.