Forearm vascular reactivity is differentially influenced by gliclazide and glibenclamide in chronically treated type 2 diabetic patients

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Abstract
Sulphonylureas (SUs) act by inhibition of beta-cell K(ATP) channels after binding to the sulphonylurea receptor SUR1. K(ATP) channels are also expressed in cardiac and vascular myocytes coupled to SUR2A and SUR2B involved into adaptations of vascular tone and myocardial contractility. Different influence of SUs on vascular function is based on different binding to the SUR family. Few data on the effect of different SUs, used in patients in therapeutic doses, on vascular function are currently available. We investigated possible effects of acute and chronic treatment with glibenclamide and gliclazide on forearm postischaemic reactive hyperaemia (RH) in type 2 diabetic patients. To that purpose a double-blind, randomized, cross-over study with gliclazide (80 mg, b.i.d.) and glibenclamide (5 mg, b.i.d.) was performed in 15 type 2 diabetic patients. Forearm vascular reactivity was measured after 5 min of ischaemia by plethysmography before and after 4 weeks treatment. After acute administration of gliclazide (80 mg) or glibenclamide (5 mg) RH was not influenced. After 4 weeks of treatment, no influence of either drug was seen in the steady state before dosing. After dosing glibenclamide induced a significant (P = 0.004) reduction of RH from 26.4 +/- 6.9 to 21.9 +/- 7.6 ml min(-1)/100 ml after 4 h. Gliclazide, conversely, did not induce a reduction of RH (23.9 +/- 6.0 to 23.3 +/- 6.6 ml min(-1)/100 ml). No influence of HbA1c or actual glycaemia on RH was observed. Our results indicate that in chronically treated patients with type 2 diabetes ingestion of glibenclamide but not gliclazide results in sustained reduction of postischaemic RH. This difference is most probably based on different SUR binding.