Lactate-Induced Vascular Relaxation in Porcine Coronary Arteries is Mediated by Ca2+-activated K+Channels

Under ischemic conditions and during strenuous exercise, lactate concentrations increase in coronary artery smooth muscle cells. Although lactate causes pH-independent vasorelaxation, the mechanisms responsible for this effect are unclear. We investigated the effect of lactate on K+channels in smooth muscle cells from porcine coronary arteries. Neutralized lactate (3–100 mm) induced vasorelaxation in ring segments of porcine coronary arteries precontracted with KCl in a dose-dependent manner. One millimolar tetraethylammonium (TEA), an inhibitor of Ca2+-activated K+channels (KCachannels), reversed the lactate-induced relaxation, while 60μmglibenclamide, an inhibitor of ATP-sensitive K+channels (KATPchannels), did not. In both inside-out and cell-attached patch clamp technique with cultured smooth muscle cells, the KCachannels were activated by lactate. In inside-out patches, lactate activated KCachannels, even under acidic conditions. This is in contrast to the effect of H+which inactivated KCachannels. We conclude that vasodilation of porcine coronary arteries induced by lactate is, at least in part, mediated by activation of KCachannels. This effect may be self-protective by maintaining coronary blood flow during ischemia.