Hemodynamic changes caused by glibenclamide in isolated, working, erythrocyte perfused rat heart.

During the past decades sulfonylurea (SU) derivatives, e.g. glibenclamide, have been extensively used in treatment of non-insulin dependent diabetes mellitus (NIDMM) (Groop, 1992). These SU derivatives exert their anti-diabetic effects by closing the socalled ATP-sensitive potassium (KATP) channels in the β-cell of the pancreas. By closing these channels membrane depolarization occurs followed by an increased Ca2+ influx and subsequent increased Ca2+ dependent exocytosis of the insulin-containing granules (Gerich, 1989). Because KATP channels not only exist in pancreatic β-cells but also in a variety of other tissues, such as vascular smooth muscle cells (Standen et al., 1989) and myocardial cells (Noma, 1983) there is reason to believe that SU derivatives may contribute to the higher mortality and morbidity by cardiovascular complications occurring in NIDDM.