Actions of cromakalim in isolated human saphenous vein.
The present study was performed to evaluate the effect of cromakalim on human vein in vitro. Branches of human saphenous vein (leftovers), obtained from patients undergoing heart revascularization surgery, were cut into rings and suspended in an organ chamber filled with Krebs-Ringer solution for the measurement of isometric contractile force. Concentration-response curves to norepinephrine and serotonin were constructed before and after pretreatment with cromakalim. The concentration-response curves to norepinephrine and serotonin were displaced to the right, and the maximal responses to both agonists were significantly inhibited by cromakalim in a concentration-dependent manner. Following sustained contraction induced by prostaglandin F2 alpha or 20 mM KCl, the cumulative addition of cromakalim to the organ chamber produced a concentration-dependent relaxation. However, in veins precontracted with 60 mM KCl the addition of cromakalim in concentrations of up to 10(-5) M did not induce relaxation. The relaxation induced by cromakalim in veins precontracted with prostaglandin F2 alpha was significantly inhibited by glibenclamide. These results indicate that cromakalim has a dilator effect in human vein that may play a helpful role in the treatment of angina. The venodilator effect of cromakalim in human saphenous vein probably involves activation of adenosine triphosphate-regulated potassium channels.