K+-CHANNEL BLOCKERS AND CORONARY VASOCONSTRICTION IN GUINEA-PIG PERFUSED HEARTS IN-VITRO

Glibenclamide, glipizide and phentolamine, three drugs which have been reported to block ATP-dependent potassium channels, increased the coronary perfusion pressure in guinea-pig isolated hearts perfused at constant flow. Blockers of other types of potassium channels, 4-aminopyridine and UK-66,914, did not significantly increase perfusion pressure. Exposing hearts to a single concentration of 3 muM glibenclamide caused a greater degree of vasoconstriction than when this was preceded by lower concentrations. The 3 muM glibenclamide-induced vasoconstriction was reduced by prazosin (1 muM), mepyramine (0.1 muM) and ranitidine (10 mum) but not by a combination of mepyramine and ranitidine or by ritanserin (0.01 muM). These results suggest that a component of the vasoconstriction induced by glibenclamide may result indirectly from the release of vasoactive mediators.