GLIBENCLAMIDE INHIBITS HYPOXIC RELAXATION OF ISOLATED PORCINE CORONARY-ARTERIES UNDER CONDITIONS OF IMPAIRED GLYCOLYSIS

The possible involvement of ATP-sensitive K+ channels (K-ATP) in hypox ic relaxation of isolated porcine coronary arteries was investigated. Tubular segments taken from the left anterior descending artery were s uspended in myographs for recording of isometric contractile force. Hy poxia (pO(2) = 20.3 mm Hg +/- 0.5) produced a greater relaxation in pr eparations contracted by 30 mM K+ (49.7% +/- 7.2) compared with 124 mM K+ (19.9% +/- 2.2) which is compatible with the involvement of K+ cha nnel activation in the mechanism of hypoxic relaxation. In a normal gl ucose-containing Krebs solution the K-ATP blocker glibenclamide (1 mu M) failed to influence the hypoxic relaxation of preparations contract ed by the thromboxane A(2) analogue U-46619. Under conditions created to inhibit non-oxidative ATP production from glycolysis using a glucos e-free Krebs solution containing 2-deoxyglucose (10 mM), the hypoxic r elaxation was enhanced from 54.5% +/- 5.0 to 77.2% +/- 4.4. Under thes e conditions glibenclamide (1 mu M) significantly inhibited the hypoxi c relaxant response from 77.2% +/- 4.2 to 55.2% +/- 4.4 and prolonged the time until half-maximal relaxation from 5.5 min +/- 0.6 to 8.1 min +/- 0.6. A low concentration of the K-ATP opener levcromakalim (30 nM ) failed to significantly potentiate the hypoxic relaxation. The adeno sine receptor blocker theophylline (1 mu M) or removal of the endothel ium showed no effect on the hypoxic relaxation. In normal glucose-cont aining Krebs solution, indomethacin (10 mu M) caused a small but signi ficant inhibition of the hypoxic relaxation from 54.5% +/- 5.0 to 41.6 % +/- 3.6. The results indicate that part of the hypoxic relaxation un der conditions of impaired glycolysis is mediated by K-ATP-channels an d that other endothelium-independent mechanisms contribute to the coro nary vascular relaxation induced by hypoxia.