Increase in the vasorelaxant potency of KATP channel opening drugs by adenosine A1 and A2 receptors in the pig coronary artery

Myograph recording from ring segments of pig small coronary arteries was used to investigate the effects of adenosine receptor activation on the vasorelaxant potency of ATP-sensitive K+ channel opening drugs. Receptor activation with 2-chloroadenosine (2-CA, 300 nM) increased the potency of both nicorandil and levcromakalim, shifting the pEC(50)s from 4.68 +/- 0.03 to 5.05 +/- 0.04 and from 6.34 +/- 0.06 to 6.72 +/- 0.06, respectively (P < 0.05 in each case). Experiments with selective adenosine receptor agonists (2-chloro-N-6-cyclopentyladenosine (CCPA), 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680)) and antagonists (8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3,a] [1,35]triazin-5-ylamino]ethyl)phenol (ZM 241385)) suggest that both A(1) and A(2a) receptors can increase the potency of nicorandil, while that of levcromakalim is increased only by A(2) receptors. Adenosine receptor activation did not affect the potency of pinacidil. Thus, adenosine receptor activation can increase the potency of some K+ channel opening drugs to relax coronary arteries, but the details of the interaction with adenosine receptors depend on the particular drug. (C) 1999 Elsevier Science B.V. All rights reserved.