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 cor onary perfusion pressure in guinea-pig isolated hearts perfused at con stant flow. Blockers of other types of potassium channels, 4-aminopyri dine and UK-66,914, did not significantly increase perfusion pressure. Exposing hearts to a single concentration of 3 muM glibenclamide caus ed a greater degree of vasoconstriction than when this was preceded by lower concentrations. The 3 muM glibenclamide-induced vasoconstrictio n 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 v asoconstriction induced by glibenclamide may result indirectly from th e release of vasoactive mediators.