The effects of levcromakalim and pinacidil on the human internal mammary artery

The present study was undertaken to examine the effects of pinacidil and levcromakalim, two potassium channel openers, on human internal mammary artery (HIMA) obtained from patients undergoing coronary artery bypass surgery, and to clarify the contribution of different K + channel subtypes in pinacidil and levcromakalim action in this blood vessel. Pinacidil and levcromakalim induced a concentration-dependent relaxation of the precontracted arterial segments (pEC 50 = 5.77 ± 0.05 and 6.89 ± 0.03, respectively). 4-Aminopyridine (3 mM), a non-selective blocker of K + channels, induced significant shifts to the right of the concentration-response curves for pinacidil and levcromakalim. Tetraethylammonium (6 mM), charybdotoxin (0.4 μM) and apamin (0.1 μM), blockers of Ca 2+ -sensitive K + channels, had no effect on the pinacidil- and levcromakalim-evoked relaxation. Glibenclamide (0.1-10 μM), a selective blocker of adenosine triphosphate (ATP)-sensitive K + channels, competitively antagonized the response to levcromakalim (pK 6 = 7.92 ± 0.07). In contrast, glibenclamide, in significantly higher concentrations (3-30 μM), non-competitively antagonized the response to pinacidil. High concentrations of pinacidil (> 10 μM ) relaxed arterial rings bathed by a medium containing 100 mM K + with maximum response 83 6%. Under the same conditions, the maximum levcromakalim-induced relaxation on HIMA was almost abolished (15 ± 2%). It is concluded that pinacidil and levcromakalim do not relax the HIMA through the same subtype of K + channel. ATP-sensitive K + channels are probably involved in levcromakalim- but not in a pinacidil-induced relaxation in the HIMA. In addition, in pinacidil-induced relaxation of the HIMA, K + channel-independent mechanisms seem to be involved.