Interaction of sulphonylurea derivatives with vascular ATP-sensitive potassium channels in humans

Diabetologia
P J BijlstraP Smits

Abstract

Cardiovascular adenosine-5'-triphosphate-sensitive potassium (KATP) channels have been reported to play an important role in endogenous cardioprotective mechanisms. Sulphonylurea derivatives can inhibit these cardioprotective mechanisms in animal models. We investigated whether therapeutic concentrations of sulphonylurea derivatives can block vascular KATP channels in humans. The forearm vasodilator responses to administration of the specific KATP channel opener diazoxide into the brachial artery of healthy male volunteers were recorded by venous occlusion plethysmography. This procedure was repeated with concomitant intraarterial infusion of:1) the sulphonylurea derivative glibenclamide (0.33 or 3.3 micrograms. min-1. dl-1, both n = 12), 2) the new sulphonylurea derivative glimepiride (2.5 micrograms.min-1. dl-1, n = 12) or 3) placebo (n = 12). The effects of glibenclamide on the vasodilator responses to sodium nitroprusside were also studied (n = 12). Glibenclamide significantly inhibited the diazoxide-induced increase in forearm blood flow ratio (ANOVA with repeated measures: p < 0.01). During the highest diazoxide dose this ratio (mean +/- SEM) was lowered from 892 +/- 165 to 449 +/- 105%, and from 1044 +/- 248 to 663 +/- 1...Continue Reading

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