DIFFERENTIAL VASORELAXANT EFFECTS OF LEVCROMAKALIM AND P1060 IN THE ISOLATED KCL-PRECONTRACTED AND RBCL-PRECONTRACTED HUMAN SAPHENOUS-VEIN - POSSIBLE INVOLVEMENT OF INTRACELLULAR CA2+ STORES

The influence of rubidium-substituted physiological salt solution (Rb-PSS) on the relaxant effects of K+ channel openers was investigated in the human saphenous vein. In tissues precontracted with 20 mM KCl (in K-PSS) levcromakalim and P1060 produced complete, sustained relaxations. However, in Rb-PSS (containing 20 mM RbCl) these effects were inhibited and, although complete relaxations still occurred, were transient. When caffeine was applied at the beginning of this fade of levcromakalim-induced relaxation in Rb-PSS its contractile effect was potentiated. Similarly, the contraction to noradrenaline was potentiated when applied at the beginning of this fade of levcromakalim-induced relaxation, whereas this response was attenuated in control tissues bathed in 20 mM KCl (in K-PSS). Our results show that the relaxant effects of K+ channel openers in human saphenous vein are inhibited in Rb-PSS, in agreement with previous studies in animal tissue, and suggest that an increased Ca2+ uptake into intracellular stores may be contributory to vasorelaxation.