Activating effects of AR-L 115 BS on the Ca2+ sensitive force, stiffness and unloaded shortening velocity (Vmax) in isolated contractile structures from mammalian heart muscle

Abstract

2-[(2-Methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS), a new positive inotropic substance, is shown to have direct activating effects upon the Ca2+ sensitive force, stiffness and unloaded shortening velocity of membrane-free, detergent-treated myocardial fibres. At pCa 6.2, application of 7--350 mumol/l AR-L 115 BS (concentrations which are also effective in living papillary muscle) led to a 30-50% increase in force and stiffness and even more in Vmax. A possible intracellular action of the drug on the contractile structures directly is discussed in comparison with the known influences of c-AMP dependent phosphorylation of myocardial regulatory proteins.