The aim was to investigate the mechanisms behind the vasodilation seen in response to acute hypoxia in porcine arteries. We hypothesized that hypoxia results in K+ channel opening in porcine large coronary arteries thereby leading to vasorelaxation.Experimental Approach
Porcine left anterior descendent coronary artery segments without endothelium were mounted in myographs for isometric tension recording. Functional studies examining the influence of K+ channels were performed and the presence of K+ channels was examined by PCR and immunoblotting.Key Results
In prostaglandin F2α (PGF2α)-contracted arteries relaxations induced by gradually reducing oxygen from 95% to 1% were associaed with lowering of smooth msucle calcium and more pronounced than in 30 mM K+-contracted arteries. The hypoxic relaxation in PGF2α-contracted arteries were inhibited by TEA, a non-specific potassium channel blocker, by iberiotoxin, a blocker of large-conductance calcium-activated K+ channels, by 4-aminopyridine, a blocker of voltage-dependent K+ channels, by glibenclamide, a blocker of ATP-sensitive K+ channels, but the largest effect was seen by XE991 and linopirdine, blockers of the Kv7.1-7.5 channels, while no effect was seen by chromanol 293B a blocker of Kv7.1. KV7.1, KV7.4, KV7.5 and the large-conductance calcium-activated BKCa channels were expressed in porcine coronary arteries.Conclusion
Our findings suggest that hypoxia induces K+ channel opening in isolated porcine coronary arteries. The effect is mainly mediated through Kv7 channels, which for the first time has been identified in porcine coronary arteries.