ADENOSINE CONTRIBUTES TO HYPOXIA-INDUCED VASODILATION THROUGH ATP-SENSITIVE K+ CHANNEL ACTIVATION

The relative contribution of adenosine and ATP-sensitive potassium (K(ATP)) channels in hypoxia-induced vasodilation was studied in isolated, saline-perfused rabbit hearts under constant flow conditions. Adenosine infusion induced a dose-dependent reduction in coronary perfusion pressure. Inhibition of K(ATP)-channels with glibenclamide (0.3 muM) significantly reduced the dilator response to adenosine (-26 +/- 6 vs. -6 +/- 2% at 1 muM), whereas those of 1 muM acetylcholine or 10 muM papaverine were unaffected. The dilator responses to the Al-receptor selective agonist, N6-cyclopentyladenosine (CPA), and the mixed A1- and A2-receptor agonist, 5'-(N-ethylcarboxamido) adenosine (NECA), were comparable to that of adenosine. Treatment with glibenclamide reduced partially but significantly the NECA-induced vasodilation (28 +/- 4 vs. -17 +/- 4%) and changed the CPA dilator response to a significant vasoconstriction. Both the nonselective adenosine-receptor antagonist, 8-phenyltheophylline (10 muM), and glibenclamide blocked the dilator response to adenosine and significantly reduced the hypoxia-induced vasodilation to the same extent. In conclusion, we suggest that the activation of K(ATP) channels plays a major role in hypoxia-induced vasodilation. A major part of this activation results from the action of adenosine on receptors closely related to the A1 type.