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


METHODS
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 microM and after 0.25 +/- 0.08 microM, p > 0.001). This effect was not evident after 90 min of venous flow conditions, 2.19 +/- 0.49 microM. 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.


CONCLUSIONS
Saphenous vein has ATP-sensitive K+ channels responsive to KCOs. The increased sensitivity to cromakalim, induced by arterial flow conditions, may represent an endogenous protective mechanism limiting ischaemic damage resulting from the higher workload imposed on grafted vein.
Beattie
D K
DK
Department of Surgery, Charing Cross & Westminster Medical School, London.
Gosling
M
M
Davies
A H
AH
Powell
J T
JT
D001158:Arteries; D001783:Blood Flow Velocity; D002839:Chromans / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010656:Phenylephrine / Q000494:pharmacology; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D002839:Chromans; D006146:Guanidines; D015221:Potassium Channels; D011759:Pyrrolidines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D010656:Phenylephrine; C075012:rilmakalim; D020110:Pinacidil; D003981:Diazoxide