Inhibition by sulphonylureas of vasorelaxation induced by K+ channel activators in vitro.
1. The effects of the sulphonylureas glibenclamide, glipizide and tolbutamide on relaxant responses to the K+ channel activator, cromakalim (BRL 34915), were investigated in rabbit isolated mesenteric artery. The interaction between glibenclamide and pinacidil, another K+ channel activator, was also studied. 2. Glibenclamide produced progressive parallel shifts to the right of the cromakalim and pinacidil concentration-response curves. The calculated pA2 values were 7.16 +/- 0.03 against cromakalim and 6.66 +/- 0.05 against pinacidil. 3. Glipizide and tolbutamide also produced parallel shifts to the right of the cromakalim concentration-response curve to yield pA2 values of 5.59 and 3.98 respectively. 4. Glibenclamide had little inhibitory effect upon vasorelaxant responses to the Ca2+ channel blocker, nifedipine. 5. The results suggest that cromakalim and pinacidil activate an ATP-sensitive K+ channel in vascular smooth muscle which may differ from that of the pancreatic beta-cells.
Wilson
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Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, Essex, UK.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004347:Drug Interactions; D005913:Glipizide / Q000494:pharmacology*; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D013453:Sulfonylurea Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; D011189:Potassium Chloride; D020110:Pinacidil; D014044:Tolbutamide; D009543:Nifedipine; D005905:Glyburide; D009638:Norepinephrine; D005913:Glipizide