Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans

被引:44
作者
Bijlstra, PJ
denArend, JACJ
Lutterman, JA
Russel, FGM
Thien, T
Smits, P
机构
[1] UNIV NIJMEGEN,DEPT PHARMACOL,NL-6500 HB NIJMEGEN,NETHERLANDS
[2] UNIV NIJMEGEN HOSP,DEPT INTERNAL MED,DIV GEN INTERNAL MED,NL-6500 HB NIJMEGEN,NETHERLANDS
关键词
ATP-sensitive potassium channels; glibenclamide; reactive hyperaemia; ischaemia; forearm blood flow;
D O I
10.1007/s001250050615
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Experimental data show that ATP-sensitive potassium (K-ATP) channels not only occur in pancreatic beta cells, but also in the cardiovascular system, where they mediate important cardioprotective mechanisms. Sulphonylurea derivatives can block the cardiovascular K-ATP channels and may therefore interfere with these cardioprotective mechanisms. Therefore, it is of clinical importance to investigate whether sulphonylurea derivatives interact with vascular K-ATP channels in humans. Using venous-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. Forearm vasodilator responses to three periods of arterial occlusion (2, 5 and 13 min) during concomitant infusion of placebo into the brachial artery were compared with responses during concomitant intra-arterial infusion of glibenclamide (0.33 mu g . min(-1). dl(-1)). A control study (n = 6) showed that time itself did not change the vasodilator response to ischaemia. Glibenclamide significantly increased minimal vascular resistance (from 2.1 +/- 0.1 to 2.3 +/- 0.2 arbitrary units, Student'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 during the first reperfusion minute (ANOVA with repeated measures: p = 0.04). In contrast, total flow debt repayment was not affected. Infusion of glibenclamide into the brachial artery resulted in local concentrations in the clinically relevant range, whereas the systemic concentration remained too low to elicit hypoglycaemic effects. Our results suggest that therapeutic concentrations of glibenclamide induce a slight but significant reduction in the early and peak vasodilation during reactive hyperaemia.
引用
收藏
页码:1562 / 1568
页数:7
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