ATP sensitive potassium channels are involved in adenosine A₂ receptor mediated coronary vasodilatation in the dog

Objective: The aim was to determine a role of ATP sensitive potassium (K_ATP) channels in adenosine A₂ receptor mediated coronary vasodilatation in anaesthetised dogs in vivo. Methods: Coronary blood flow in the left circumflex coronary artery, aortic pressure, and left ventricular pressure were measured during intracoronary infusions of the drugs into the left circumflex artery. Results: A non-selective A₂ receptor agonist NECA (5'-N-ethylcarboxamidoadenosine) at 10^-10-10^-8 mol·min^-1 before and after an A, receptor antagonist DPCPX (8-cyclopentyl-l,3-dipropylxanthine) increased coronary blood flow in a dose dependent manner, without affecting other haemodynamic variables. Glibenclamide at 10 μg·kg^-1·min^-1, which did not alter baseline haemodynamic variables, markedly inhibited the increases in coronary blood flow caused by NECA alone and after DPCPX (p<0.01). A non-selective adenosine receptor antagonist 8-phenyltheophylline abolished the NECA induced increases in coronary blood flow after DPCPX. These results suggest that A₂ receptor mediated coronary vasodilatation was mediated largely by opening of K_ATP channels. Glibenclamide did not alter the increase in coronary blood flow evoked by forskolin or acetylcholine, suggesting that K_ATP channels may not be involved in coronary vasodilatation induced by activation of adenylate cyclase or guanylate cyclase. Furthermore, DPCPX increased basal coronary blood flow, which was blocked by 8-phenyltheophylline and by glibenclamide, suggesting that it may have unmasked A₂ receptor mediated coronary vasodilatation by inhibiting the A₁ receptor mediated vasoconstricting action of endogenous adenosine. Conclusions: Opening of K_ATP channels may be involved importantly in adenosine A₂ receptor mediated coronary vasodilatation in canine hearts.Cardiovascular Research 1994:28:906-911.