Hm. Prior et al., Role of K+ channels in A(2A) adenosine receptor-mediated dilation of the pressurized renal arcuate artery, BR J PHARM, 126(2), 1999, pp. 494-500
1 Adenosine A(2A) receptor-mediated renal vasodilation was investigated by
measuring the lumenal diameter of pressurized renal arcuate arteries isolat
ed from the rabbit.
2 The selective A(2A) receptor agonist CGS21680 dilated the arteries with a
n EC50 of 130 nM. The CGS21680-induced vasodilation was, on average, 34% le
ss in endothelium-denuded arteries.
3 The maximum response and the EC50, for CGS21680-induced vasodilation in e
ndothelium-intact arteries were not significantly affected by incubation wi
th the K+ channel blockers apamin (100 nM, iberiotoxin (100 nM), 3,4-diamin
opyridine (1 mM), glibenclamide (1 mu M) or Ba2+ (10 mu M). However, a cock
tail mixture of these blockers did significantly inhibit the maximum respon
se by almost 40%, and 1 mM Ba2+ alone or 1 mM Ba2+ in addition to the cockt
ail inhibited the maximum CGS21680-response by 58% and about 75% respective
ly.
4 CCS21680-induced vasodilation was strongly inhibited when the extracellul
ar 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 inhibi
tor of Na+/K+-ATPase, but ouabain had a similar inhibitory effect on vasodi
lation 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) rec
eptor-mediated renal vasodilation. The inhibitory effect of raised extracel
lular K+ levels on the A(2A) response may be due to K+-induced stimulation
of Na+/K+-ATPase.