Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans
Abstract
Experimental data show that ATP-sensitive potassium (KATP) 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 KATP channels and may therefore interfere with these cardioprotective mechanisms. Therefore, it is of clinical importance to investigate whether sulphonylurea derivatives interact with vascular KATP 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 microgram.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 ...Continue Reading
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Inhibition of vascular ATP-sensitive K+ channels does not affect reactive hyperemia in human forearm
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