Hypoxic dilatation of porcine small coronary arteries: Role of endothelium and K-ATP-channels

1. The aim of the present study was to determine the cellular mechanims and potential mediators involved in hypoxic dilatation of porcine small coronary arteries. 2 Small coronary arteries were isolated from a branch of the left anterior descending artery of porcine hearts, cannulated with glass micropipettes and studied in a perfusion myograph system. At a transmural pressure of 40 mmHg, the arteries had an internal diameter of 167.8 +/- 6.6 mu m (n = 37). 3 In arteries contracted with acetylcholine (ACh), hypoxia (0% O-2, 30 min) caused dilatation (86.9 +/- 6.7% relaxation, n = 6) in vessels with endothelium but constriction in endothelium-denuded vessels. 4 Hypoxic vasodilatation occurring in arteries with endothelium was abolished by the K-aTp channel inhibitor, glibenclamide (0.44 mu M), but was not affected by inhibition of nitric oxide synthase (L-NAME, 44 mu M) or cyclo-oxygenase (indomethacin, 4.4 mu M). 5 Bradykinin evoked endothelium-dependent relaxation that was inhibited by L-NAME (44 mu M) but not glibenclamide 0.44 mu M). Cromakalim (0.1 - 0.3 mu M), a K-ATP channel opener, caused relaxation that was inhibited by glibenclamide, but was not affected by L-NAME (44 mu M) and/or indomethacin (4.4 mu M). 6 Endothelium-removal inhibited vasodilatation evoked by cromakalim, but increased vasodilator responses to the NO donor, SIN-1 (10(-8) to 10(-5) M). 7 These results indicate that hypoxia acted directly on vascular smooth muscle of small coronary arteries to cause contraction. However, this effect was overwhelmed by endothelium-dependent relaxation in response to hypoxia. This relaxation was most likely mediated by release of an endothelium-derived factor, distinct from nitric oxide or prostacyclin, that activated smooth muscle K-ATP-channels.