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 microM glibenclamide caused a greater degree of vasoconstriction than when this was preceded by lower concentrations. The 3 microM glibenclamide-induced vasoconstriction was reduced by prazosin (1 microM), mepyramine (0.1 microM) and ranitidine (10 microM) but not by a combination of mepyramine and ranitidine or by ritanserin (0.01 microM). These results suggest that a component of the vasoconstriction induced by glibenclamide may result indirectly from the release of vasoactive mediators.