ACUTE EFFECTS OF ORAL GLIBENCLAMIDE ON BLOOD-PRESSURE AND FOREARM VASCULAR-RESISTANCE IN DIABETICS (VOL 24, PG 333, 1997)

1. To determine the effects of an acute oral dose of glibenclamide on blood pressure (BP), basal forearm vascular resistance (FVR) and FVR r esponses to the K-ATP(+) channel activating vasodilator diazoxide, a p lacebo-controlled, double-blind cross-over study was performed in eigh t male volunteers with non-insulin-dependent diabetes mellitus, 2. Cha nges in vascular responses to progressively increasing concentrations of diazoxide (3.75-30 mg/kg per min) and noradrenaline (25-100 ng/kg p er min) were measured by venous occlusion plethysmography. 3. Glibencl amide significantly lowered plasma glucose levels compared with placeb o (P<0.02) and attenuated the decrease in FVR (P<0.05) and the decreas e in systolic RP (P<0.05) that followed a meal, However, vasodilator r esponses to diazoxide were potentiated by the administration of oral g libenclamide (P<0.01), 4. Acute administration of oral glibenclamide a ttenuates the normal decrease in FVR and systolic BP that follows a me al and potentiates rather than inhibits forearm vasodilator responses to intra-arterial diazoxide, probably via indirect humoral effects. Th ese results suggest that glibenclamide has direct or indirect vasocons trictor effects that antagonize the normal increase in forearm blood f luff that follows a meal and that the inhibition of vascular K-ATP(+) channels following acute oral glibenclamide administration is clinical ly insignificant compared with other indirect vascular effects of the drug.