Hypoglycemic sulfonylureas antagonize the effects of cromakalim and pinacidil on 86Rb fluxes and contractile activity in the rat aorta.
Cromakalim, pinacidil and nitroprusside provoked concentration-dependent relaxations of K(+)-depolarized rat aortae. Glibenclamide, tolbutamide and to a lesser extent tetraethylammonium antagonized the vasorelaxant action of cromakalim and pinacidil. Cromakalim, pinacidil but not nitroprusside elicited a marked increase in 86Rb outflow from preloaded and perifused aortic rings. These increases in 86Rb outflow were inhibited in a concentration-dependent manner by glibenclamide and tetraethylammonium. Our data extend previous observations indicating the involvement of K+ channels in the vasorelaxant properties of cromakalim and pinacidil. Moreover, the present findings suggest that both compounds could interfere with a vascular type of ATP-sensitive K+ channels.
Lebrun
P
P
Laboratory of Pharmacology, Faculty of Medicine and Pharmacy, Brussels Free University, Belgium.
Fang
Z Y
ZY
Antoine
M H
MH
Herchuelz
A
A
Hermann
M
M
Berkenboom
G
G
Fontaine
J
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001578:Benzopyrans / Q000037:antagonists & inhibitors*; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000037:antagonists & inhibitors*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D006146:Guanidines; D007004:Hypoglycemic Agents; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D013453:Sulfonylurea Compounds; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D020110:Pinacidil; D014044:Tolbutamide; D005905:Glyburide