Experimental data suggest that vascular ATP-sensitive potassium (KATP) channels may be an important determinant of functional hyperaemia, but the contribution of KATP 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 KATP channel inhibitors glibenclamide (at two different doses: 15 and 100µg/min) and gliclazide (at 300µg/min). FHBF was induced by 2min of non-ischaemic wrist flexion–extension exercise at 45 cycles/min. Compared with vehicle (isotonic saline), glibenclamide at either 15µg/min or 100µg/min did not significantly alter resting forearm blood flow or peak FHBF. The blood volume repaid at 1 and 5min 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±1.3m-units/l; P = 0.02) and 150% (from 9.1±1.3 to 22.9±3.5m-units/l; P = 0.002) after the 15 and 100µg/min infusions respectively. Gliclazide also did not affect resting forearm blood flow, peak FHBF, or the blood volume repaid at 1 and 5min 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 KATP channels with glibenclamide or gliclazide does not appear to affect resting forearm blood flow or FHBF in healthy humans. These findings suggest that vascular KATP channels may not play an important role in regulating basal vascular tone or skeletal muscle metabolic vasodilation in the forearm of healthy human subjects.
Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm
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H.M. Omar FAROUQUE, Ian T. MEREDITH; Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm. Clin Sci (Lond) 1 January 2003; 104 (1): 39–46. doi: https://doi.org/10.1042/cs1040039
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