Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm

Experimental data suggest that vascular ATP-sensitive potassium (K-ATP) channels may be an important determinant of functional hyperaemia, but the contribution of K-ATP channels to exercise-induced hyperaemia in humans is unknown. Forearm blood flow was assessed in 39 healthy subjects (23 males/16 females; age 22 +/- 4 years) using the technique of venous occlusion plethysmography. Resting forearm blood flow and functional hyperaemic blood flow (FHBF) were measured before and after brachial artery infusion of the K-ATP channel inhibitors glibenclamide (at two different doses: 15 and 100 mug/min) and gliclazide (at 300 mug/min). FHBF was induced by 2 min of non-ischaemic wrist flexion-extension exercise at 45 cycles/min. Compared with vehicle (isotonic saline), glibenclamide at either 15 mug/min or 100 mug/min did not significantly alter resting forearm blood flow or peak FHBF. The blood volume repaid at 1 and 5 min after exercise was not diminished by glibenclamide. Serum glucose was unchanged after glibenclamide, but plasma insulin rose by 36% (from 7.2 +/- 0.8 to 9.8+/-1.3 m-units/l; P = 0.02) and 150% (from 9.1 +/- 1.3 to 22.9 +/- 3.5 m-units/l; P = 0.002) after the 15 and 100 mug/min infusions respectively. Gliclazide also did not affect resting forearm blood flow, peak FHBF, or the blood volume repaid at 1 and 5 min after exercise, compared with vehicle (isotonic glucose). Gliclazide induced a 12% fall in serum glucose (P = 0.009) and a 38% increase in plasma insulin (P = 0.001). Thus inhibition of vascular K-ATP channels with glibenclamide or gliclazide does not appear to affect resting forearm blood flow or FHBF in healthy humans. These findings suggest that vascular K-ATP channels may not play an important role in regulating basal vascular tone or skeletal muscle metabolic vasodilation in the forearm of healthy human subjects.