Pj. Bijlstra et al., BLOCKADE OF VASCULAR ATP-SENSITIVE POTASSIUM CHANNELS REDUCES THE VASODILATOR RESPONSE TO ISCHEMIA IN HUMANS, Diabetologia, 39(12), 1996, pp. 1562-1568
Citations number
50
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Experimental data show that ATP-sensitive potassium (K-ATP) channels n
ot only occur in pancreatic beta cells, but also in the cardiovascular
system, where they mediate important cardioprotective mechanisms. Sul
phonylurea derivatives can block the cardiovascular K-ATP channels and
may therefore interfere with these cardioprotective mechanisms. There
fore, it is of clinical importance to investigate whether sulphonylure
a derivatives interact with vascular K-ATP channels in humans. Using v
enous-occlusion strain-gauge plethysmography, we investigated whether
ischaemia-induced reactive hyperaemia is reduced by the sulphonylurea
derivative glibenclamide in 12 healthy male non-smoking volunteers. Fo
rearm vasodilator responses to three periods of arterial occlusion (2,
5 and 13 min) during concomitant infusion of placebo into the brachia
l artery were compared with responses during concomitant intra-arteria
l infusion of glibenclamide (0.33 mu g . min(-1). dl(-1)). A control s
tudy (n = 6) showed that time itself did not change the vasodilator re
sponse to ischaemia. Glibenclamide significantly increased minimal vas
cular resistance (from 2.1 +/- 0.1 to 2.3 +/- 0.2 arbitrary units, Stu
dent's t-test: p = 0.01), and reduced mean forearm blood flow (from 37
.5 +/- 2.0 to 35.4 +/- 2.0 mi min(-1). dl(-1) after 13 min occlusion,
ANOVA with repeated measures: p = 0.006) and flow debt repayment durin
g the first reperfusion minute (ANOVA with repeated measures: p = 0.04
). In contrast, total flow debt repayment was not affected. Infusion o
f glibenclamide into the brachial artery resulted in local concentrati
ons in the clinically relevant range, whereas the systemic concentrati
on remained too low to elicit hypoglycaemic effects. Our results sugge
st that therapeutic concentrations of glibenclamide induce a slight bu
t significant reduction in the early and peak vasodilation during reac
tive hyperaemia.