THE EFFECT OF ATP-SENSITIVE POTASSIUM (KATP )
CHANNEL IHIBITION ON METABOLIC VASODILATION IN HUMAN SKELETAL MUSCLE
VASCULATURE. H.M.O.
Farouque*, R.A.P. Skyrme-Jones, M.J.
Zhang, R.C. O'Brien & I.T. Meredith. Centre for Heart & Chest Research,
Monash University, Monash Medical Centre, Melbourne. Recent data
suggests that endothelium-dependent vasodilators such as nitric oxide and
prostacyclin are important determinants or resting and metabolic vasodilation
in human skeletal muscle vasculature. Experimental evidence suggests that KATP
channels may also play a role
although little is known of this in humans. We therefore assessed the
contribution of KATP channels in the regulation of resting,
ischaemia-induced and exercise-induced hyperaemia in the human forearm using
the technique of venous occlusion plethysmography in 9 healthy subjects (age
22±5 years, mean ± SD; 8M, 1F). Resting
forearm blood flow (FBF), reactive hyperaemic blood flow IRHBF, in response to
ischaemia induced by 5 minutes of suprasystolic cuff inflation on the upper
arm) and exercise-induced functional hyperaemia (FHBF induced by 2 minutes of
wrist flexion and extension exercise at 45 cycles per minute) were assessed
before and after intra-arterial infusion of glibenclamide (glib) at a dose of
15mg/minute for 10 minutes. The
dose was calculated to attain a desired intra-arterial concentration of
500ng/ml. Compared to vehicle infusion
(0.9% saline), glib did not effect FBF (2.0±0.2 vs 2.0±0.2 ml*100ml forearm -1
* min -1 ), peak RHBF (21.4 ± 2.5 vs 21.5±2.8 ml*100ml forearm -1*
min -1). or peak FHBF (19.7 ±1.9 vs 19.3 ± 1.5 ml*100ml forearm -1
* min -1). The volume of
blood repaid o the forearm (calculated from the area under the flow-time curve)
following ischaemia and exercise was not diminished by glib. Glib did not alter
resting heart rate (59.2±2.1 vs 61.1±1.8lbpm) or mean arterial blood pressure
(80.6±1.8 vs 80.9 ± 1.8mmHg) but plasma glucose was reduced by 23%
(p<0.001), insulin increased by 74% (p<0.01) and C-peptide levels increased
by 32% (p<0.05). Conclusion: Glib, a KATP channel antagonist
commonly utilised in the management of type 2 diabetes, does not appear to
effect FBF, ischaemia-induced or exercise-induced hyperaemia in the human
forearm circulation in healthy subjects in conventionally used doses. Whether
metabolic vasodilation would be impaired by KATP channel inhibition
in the setting of impaired NO-mediated or prostacyclin-mediated vasodilation
needs to be investigated.
