Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat.
1. In rat isolated thoracic aortic rings pre-contracted with noradrenaline (10(-6) M), cromakalim (3 x 10(-7)-3 x 10(-5) M) produced concentration-related relaxation. This effect was progressively inhibited by increasing concentrations of the anti-diabetic sulphonylurea drug, glibenclamide (10(-6)-10(-5) M). 2. In rat isolated portal veins, cromakalim (3 x 10(-8)-10(-6) M) produced concentration-related inhibition of the spontaneous contractive activity and glibenclamide (3 x 10(-7)-3 x 10(-6) M) prevented this inhibitory action in a concentration-dependent manner. 3. In both rat aortic rings and portal veins, cromakalim (10(-5) M) stimulated 86Rb efflux. Prior exposure to glibenclamide (10(-7)-10(-6) M) produced a concentration-related inhibition of this response. 4. In conscious rats, cromakalim, 0.075 mg kg-1 i.v., produced a rapid and sustained fall in arterial blood pressure which was not influenced by pretreatment (2 h) with a large oral dose of glibenclamide (100 mg kg-1). 5. In conscious rats, the hypotensive action of cromakalim, 0.075 mg kg-1 i.v., was abolished by pretreatment (30 min) with glibenclamide, 20 mg kg-1, given by the intravenous route. 6. The results suggest that the vasorelaxant and hypotensive actions of cromakalim involve a K+ channel which can be inhibited by glibenclamide, but which may be distinct from the ATP-sensitive K+ channel of the pancreatic beta-cell.
Buckingham
R E
RE
Beecham Pharmaceuticals, Research Division, Medicinal Research Centre, Essex.
Hamilton
T C
TC
Howlett
D R
DR
Mootoo
S
S
Wilson
C
C
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001578:Benzopyrans / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010276:Parasympatholytics / Q000037:antagonists & inhibitors*; D011169:Portal Vein / Q000187:drug effects; D011758:Pyrroles / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes
D001578:Benzopyrans; D010276:Parasympatholytics; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D019806:Cromakalim; D005905:Glyburide