EFFECT OF TRANDOLAPRILATE AND VERAPAMIL O N GLUCOSE-TRANSPORT AND GLUCOSE-TRANSPORTER (GLUT-1, GLUT-4) IN LANGENDORFF-RAT HEARTS

The effects of the ACE-inhibitor trandolaprilate and the Ca++-antagoni st verapamil on glucose transport and carrier-translocation (GLUT-1,GL UT-4) were measured in isolated Langendorff-hearts of male Wistar rats and compared with known insulin effects. Trandolaprilate (TRA 10(-4) M) and verapamil (VERA 10(-7) M) were administered alone and in combin ation (TRA 10(-5) M/VERA 10(-8) M) at concentrations which did not inc rease coronary flow. Insulin was employed at maximally glucose-transpo rt-effective concentration (8 x 10(-8) M). Trandolaprilate stimulated glucose transport, measured as (C-14)3-0-methyl-glucose elution, and c arrier-translocation, measured as GLUT-1/GLUT-4 protein content in sub cellular membrane fractions by western blot. Despite constant perfusio n, trandolaprilate increased both contractility (dp/dt(max)) as well a s relaxation (lime constant T). thus the observed effect could be seco ndary to altered cardiac performance. Verapamil did not change glucose transport while contractility was decreased and relaxation increased. The combination with trandolaprilate attenuated the metabolic effect of the ACE-inhibitor. A combination of trandolaprilate and verapamil m ap be beneficial because of possible synergistic effects of both metab olic and hemodynamic effects of both drugs. Essential sentence: Indepe ndent of coronary perfusion, trandolaprilate exerts a functional incre ase in membrane glucose transport and a structural increase in carrier translocation, whereas verapamil is neutral.