Sum m ary Sulphonylurea derivatives are widely used in the treatment of non-insulin-dependent diabetes mellitus. The mechanism of action of the insulinotropic effect of these agents is based on the closure of adenosine-S'-triphosphate (ATP)-sensitive potas sium channels (KATP-channels) in the beta cells of the pancreas. In the last decade, these KATP-channels have been demonstrated in myocardial cells as well as in vascular smooth muscle cells. During myocardi al ischaemia, the KATP-channels are thought to open by a fall in the cytosolic ATP concentration. The in crease in the extracellular adenosine concentration, and the release of endothelium-derived hyperpolarizing factor (EDHF) during ischaemia may further contribute to the opening of cardiovascular KAXPchannels. Independently from the mechanism of opening, sulphonylurea derivatives have been report ed to block the opening of cardiovascular KATP-channels. Related to the role of KATP-channel~opening in the (patho)physiology of ischaemia, the use of sul phonylurea derivatives significantly modifies the out come of experimental myocardial infarction. Sulpho nylurea derivatives impair the recovery of the con tractile function and increase the ultimate infarct size in animal models. In contrast, sulphonylurea de rivatives have a beneficial effect on the incidence of ventricular fibrillation as occurs after ischaemic inci dents of the myocardium. Based on these experimen tal observations, human studies are indicated to in vestigate whether the use of these drugs modifies the clinical outcome of cardiovascular events in patients with non-insulin dependent diabetes mellitus. [Dia betologia (1995)38:116-121] Key w ords Sulphonylurea derivatives, potassium channels, cardiovascular system, adverse effects, ischaemia.Non-insulin-dependent diabetes mellitus (NIDDM) accounts for about 85 % of all cases of diabetes melli tus, and has been reported to be an important risk factor for cardiovascular morbidity and mortality [1][2][3]. Up to now, oral hypoglycaemic drugs, in particu lar sulphonylurea derivatives, have represented the backbone of NIDDM therapy for the last decades [4,5]. The beneficial metabolic effects of sulphonylurea Abbreviations: KAT1 ,-channel, Adenosine-5'-triphosphate de pendent potassium channel; EDHF, endothelium-derived hyperpolarizing factor; NIDDM, non-insulin dependent diabe tes mellitus.
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