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.
Gwilt
M
M
Cardiovascular Department, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
Orme
J
J
Rourke
J D
JD
Henderson
C G
CG
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D005913:Glipizide / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D015221:Potassium Channels; D011719:Pyrazines; D011725:Pyridines; C069454:UK 66914; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D005905:Glyburide; D005913:Glipizide; D010646:Phentolamine