The effects of potassium channel openers on saphenous vein exposed to arterial flow

Objectives: To assess the sensitivity of saphenous vein to potassium channel opening drugs (KCOs). Methods: Saphenous vein, harvested at bypass surgery or high ligation for correction of varicose veins, was exposed to an in vitro flow circuit and vasomotor responses assessed by organ bath pharmacology. Outcome measures: Effective drug concentrations for 50% reduction in vein ring tension (IC50). Results: Vein rings pre-contracted with phenylephrine showed a concentration-dependent relaxation to all the KCOs tested with a potency ranking of HOE 234 > cromakalim > pinacidil > diazoxide. The relaxation to cromakalim was endothelium-independent and was inhibited by glibenclamide (an ATP-sensitive K+ channel blocker). The sensitivity of vein rings to cromakalim increased after exposure to arterial flow conditions for 90 minutes (IC50 before 1.7 ± 0.25 μM and after 0.25 ± 0.08 μM, p > 0.001). This effect was not evident after 90 min of venous flow conditions, 2.19 ± 0.49 μM. When the workload on vein, exposed to arterial flow conditions, was reduced mechanically by external stenting with PTFE the increased sensitivity to cromakalim was abolished. Conclusion: Saphenous vein has ATP-sensitive K+ channels responsive to KCOs. The increased sensitivity to cromakalim, induced by arterial flow conditions, may represent and endogenous protective mechanism limiting ischaemic damage resulting from the higher workload imposed on grafted vein