Inhibition by sulphonylureas of vasorelaxation induced by K+ channel activators in vitro

Abstract

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.